A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
The procedures involved in combining separately developed modules, components, or subsystems so that they work together as a complete system. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The portion of an interactive computer program that issues messages to and receives commands from a user.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
Collections of facts, assumptions, beliefs, and heuristics that are used in combination with databases to achieve desired results, such as a diagnosis, an interpretation, or a solution to a problem (From McGraw Hill Dictionary of Scientific and Technical Terms, 6th ed).
Unequal cell division that results in daughter cells of different sizes.
Progenitor cells from which all blood cells derive.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.
The technique of using FIXATIVES in the preparation of cytologic, histologic, or pathologic specimens for the purpose of maintaining the existing form and structure of all the constituent elements.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A parasexual process in BACTERIA; ALGAE; FUNGI; and ciliate EUKARYOTA for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a uni-directional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes.
Deoxyribonucleic acid that makes up the genetic material of bacteria.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses.
The full collection of microbes (bacteria, fungi, virus, etc.) that naturally exist within a particular biological niche such as an organism, soil, a body of water, etc.
Decrease in existing BODY WEIGHT.
A collective genome representative of the many organisms, primarily microorganisms, existing in a community.
Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).
A publication issued at stated, more or less regular, intervals.
The branch of science concerned with the interrelationship of organisms and their ENVIRONMENT, especially as manifested by natural cycles and rhythms, community development and structure, interactions between different kinds of organisms, geographic distributions, and population alterations. (Webster's, 3d ed)
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
A technique used to separate particles according to their densities in a continuous density gradient. The sample is usually mixed with a solution of known gradient materials and subjected to centrifugation. Each particle sediments to the position at which the gradient density is equal to its own. The range of the density gradient is usually greater than that of the sample particles. It is used in purifying biological materials such as proteins, nucleic acids, organelles, and cell types.
A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes.
A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).
Messages between computer users via COMPUTER COMMUNICATION NETWORKS. This feature duplicates most of the features of paper mail, such as forwarding, multiple copies, and attachments of images and other file types, but with a speed advantage. The term also refers to an individual message sent in this way.
The study of natural phenomena by observation, measurement, and experimentation.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
Tumors or cancer of the DIGESTIVE SYSTEM.
Diseases in any part of the GASTROINTESTINAL TRACT or the accessory organs (LIVER; BILIARY TRACT; PANCREAS).
NATIONAL LIBRARY OF MEDICINE service for health professionals and consumers. It links extensive information from the National Institutes of Health and other reviewed sources of information on specific diseases and conditions.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis.
A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain.
Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver.
Vesicles formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein CLATHRIN. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as ENDOSOMES.
Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.

A cytomegalovirus glycoprotein re-routes MHC class I complexes to lysosomes for degradation. (1/6965)

Mouse cytomegalovirus (MCMV) early gene expression interferes with the major histocompatibility complex class I (MHC class I) pathway of antigen presentation. Here we identify a 48 kDa type I transmembrane glycoprotein encoded by the MCMV early gene m06, which tightly binds to properly folded beta2-microglobulin (beta2m)-associated MHC class I molecules in the endoplasmic reticulum (ER). This association is mediated by the lumenal/transmembrane part of the protein. gp48-MHC class I complexes are transported out of the ER, pass the Golgi, but instead of being expressed on the cell surface, they are redirected to the endocytic route and rapidly degraded in a Lamp-1(+) compartment. As a result, m06-expressing cells are impaired in presenting antigenic peptides to CD8(+) T cells. The cytoplasmic tail of gp48 contains two di-leucine motifs. Mutation of the membrane-proximal di-leucine motif of gp48 restored surface expression of MHC class I, while mutation of the distal one had no effect. The results establish a novel viral mechanism for downregulation of MHC class I molecules by directly binding surface-destined MHC complexes and exploiting the cellular di-leucine sorting machinery for lysosomal degradation.  (+info)

Identification of low density lipoprotein receptor-related protein-2/megalin as an endocytic receptor for seminal vesicle secretory protein II. (2/6965)

The low density lipoprotein receptor-related protein-2/megalin (LRP-2) is an endocytic receptor that is expressed on the apical surfaces of epithelial cells lining specific regions of the male and female reproductive tracts. In the present study, immunohistochemical staining revealed that LRP-2 is also expressed by epithelial cells lining the ductal region and the ampulla of the rat seminal vesicle. To identify LRP-2 ligands in the seminal vesicle, we probed seminal vesicle fluid with 125I-labeled LRP-2 in a gel-blot overlay assay. A 100-kDa protein (under non-reducing conditions) was found to bind the radiolabeled receptor. The protein was isolated and subjected to protease digestion, and the proteolytic fragments were subjected to mass spectroscopic sequence analysis. As a result, the 100-kDa protein was identified as the seminal vesicle secretory protein II (SVS-II), a major constituent of the seminal coagulum. Using purified preparations of SVS-II and LRP-2, solid-phase binding assays were used to show that the SVS-II bound to the receptor with high affinity (Kd = 5.6 nM). The binding of SVS-II to LRP-2 was inhibited using a known antagonist of LRP-2 function, the 39-kDa receptor-associated protein RAP. Using a series of recombinant subfragments of SVS-II, the LRP-2 binding site was mapped to a stretch of repeated 13-residue modules located in the central portion of the SVS-II polypeptide. To evaluate the ability of LRP-2 to mediate 125I-SVS-II endocytosis and lysosomal degradation, ligand clearance assays were performed using differentiated mouse F9 cells, which express high levels of LRP-2. Radiolabeled SVS-II was internalized and degraded by the cells, and both processes were inhibited by antibodies to LRP-2 or by RAP. The results indicate that LRP-2 binds SVS-II and can mediate its endocytosis leading to lysosomal degradation.  (+info)

Purification of gibberellic acid-induced lysosomes from wheat aleurone cells. (3/6965)

Using isopycnic density gradient centrifugation, lysosomes were concentrated in a single region of a sucrose-Ficoll gradient (p = 1-10 g cm-3), well separated from most other cell organelles. Gibberellic acid-induced lysosomes were found to be rich in alpha-amylase and protease but not ribonuclease. The lysosomal band also contained a majority of the NADH2-cytochrome c reductase, a marker enzyme for endoplasmic reticulum, found in the gradient. Examination of electron micrographs revealed that a purified band of lyosomes contained at least 3 vesicle types, ranging in size from 0-1 to 0-5 mum. The significance of these findings to proposed mechanisms of action of gibberellic acid is discussed.  (+info)

Impaired lysosomal processing of beta2-microglobulin by infiltrating macrophages in dialysis amyloidosis. (4/6965)

BACKGROUND: Macrophages may participate in amyloid fibril formation by processing the protein precursor. Although this theory seems to apply for amyloidosis, in which proteolytic cleavage is a prerequisite for amyloid fibril formation, it has not been demonstrated for beta2-microglobulin (beta2m) amyloidosis. We aimed to establish the role played by macrophages in beta2m amyloidosis. METHODS: We used a double immunogold electron microscopy technique, including mouse antihuman CD68, rabbit antihuman beta2m, amyloid P component, and lysosome-associated membrane protein (LAMP-1) antibodies. Differential density labeling studies of beta2m and amyloid P component were performed extra- and intracellularly to assess protein processing by macrophages. RESULTS: The cells surrounding amyloid fibrils were found to be mostly CD68 positive, suggesting that they were of monocyte-macrophage lineage. Intracellular accumulation of amyloid fibrils was also observed; these fibrils were constantly surrounded by LAMP-1-linked gold particles, demonstrating that intracellular beta2m was almost exclusively lysosomal. The rough-surface endoplasmic reticulum was not labeled by beta2m antibody, suggesting that there was no active synthesis of beta2m by the cells. As a marker of endocytosis, protruded cytoplasmic processes in close relation with the intracellular accumulations of beta2m amyloid fibrils were observed. No difference in density labeling (extracellular vs. intracellular) was observed for beta2m, whereas intracellular P component labeling was significantly decreased. CONCLUSIONS: All of these data are strongly suggestive of phagocytosis and not synthesis of amyloid fibrils by macrophages. Further, they demonstrate an impaired lysosomal processing specific for beta2m, as other compounds of the amyloid fibrils (P component) are significantly cleared.  (+info)

5'-Nucleotidase activity of mouse peritoneal macrophages. II. Cellular distribution and effects of endocytosis. (5/6965)

The diazonium salt of sulfanilic acid (DASA) can inactivate about 80% of the total 5'-nucleotidase of viable macrophages. The remaining 20% can be inactivated if the cells are first lysed in detergent, and presumably represents an intracellular pool of 5'-nucleotidase. The bulk of this pool may represent cytoplasmic vesicles derived from plasma membrane by endocytosis. This internal compartment is expanded up to threefold immediately after the cells have ingested a large latex load. This is consistent with previous observations on the internalization of 5'-nucleotidase in latex phagosomes. In latex-filled cells this intracellular pool of enzyme is inactivated over a few hours, and the cells then slowly increase their enzyme activity to nearly normal levels. However, 24 h after latex ingestion the metabolism of 5'-nucleotidase in these recovered cells is abnormal, as the rate of enzyme degradation is about twice the normal rate, and the DASA-insensitive enzyme pool in these cells is strikingly diminished. This may reflect effects of the accumulated indigestible particles on the fate of incoming pinocytic vesicles or on newly synthesized plasma membrane precursor. Another endocytic stimulus, concanavalin A, also reduces the total cell 5'-nucleotidase activity. This effect, which is time and temperature dependent, can be prevented by the competitive sugar alpha-methyl mannose. The concanavalin A inhibition can be reversed in the absence of new protein synthesis or in cells cultivated in serum-free conditions. It is not known whether the effect of concanavalin A on 5'-nucleotidase depends upon the interiorizaiton of plasma membrane or is strictly associated with events at the cell surface.  (+info)

Macrophage plasminogen activator: induction by asbestos is blocked by anti-inflammatory steroids. (6/6965)

Intraperitoneal injection of asbestos fibres into mice induces the formation of exudates containing macrophages that produce plasminogen activator. Like-wise, in vitro addition of asbestos to macrophage cultures stimulates plasminogen activator secretion; the synthesis and secretion of lysozyme and lysosomal enzymes are not changed under these conditions. The enhanced secretion of plasminogen activator by macrophages exposed to asbestos is suppressed by low concentrations of anti-inflammatory steroids.  (+info)

Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments. (7/6965)

MHC class II molecules exert their function at the cell surface by presenting to T cells antigenic fragments that are generated in the endosomal pathway. The class II molecules are targetted to early lysosomal structures, termed MIIC, where they interact with antigenic fragments and are subsequently transported to the cell surface. We previously visualised vesicular transport of MHC class II-containing early lysosomes from the microtubule organising centre (MTOC) region towards the cell surface in living cells. Here we show that the MIIC move bidirectionally in a 'stop-and-go' fashion. Overexpression of a motor head-deleted kinesin inhibited MIIC motility, showing that kinesin is the motor that drives its plus end transport towards the cell periphery. Cytoplasmic dynein mediates the return of vesicles to the MTOC area and effectively retains the vesicles at this location, as assessed by inactivation of dynein by overexpression of dynamitin. Our data suggest a retention mechanism that determines the perinuclear accumulation of MIIC, which is the result of dynein activity being superior over kinesin activity. The bidirectional nature of MIIC movement is the result of both kinesin and dynein acting reciprocally on the MIIC during its transport. The motors may be the ultimate targets of regulatory kinases since the protein kinase inhibitor staurosporine induces a massive release of lysosomal vesicles from the MTOC region that is morphologically similar to that observed after inactivation of the dynein motor.  (+info)

Endometrial lysosomal enzyme activity in normal cycling endometrium. (8/6965)

The objective of this study was to evaluate the possible role of four lysosomal enzymes in endometrial function and remodelling during the normal menstrual cycle by fluorimetric measurement (acid phosphatase, N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and alpha-D-mannosidase). A prospective study was conducted of 45 endometrial biopsies obtained from women with normal menstrual cycles. Activity of all four enzymes was identified in human endometrium. Activity of acid phosphatase and N-acetyl-beta-D-glucosaminidase was relatively high, whilst that of alpha-L-fucosidase and alpha-D-mannosidase was low. There was no significant change in the activity of any of the four enzymes from the proliferative to the secretory phase of the cycle. This study suggests that the activity of these enzymes remains constant throughout a major portion of the normal cycle.  (+info)

TY - JOUR. T1 - Regulators of lysosome function and dynamics in Caenorhabditis elegans. AU - Gee, Kevin. AU - Zamora, Danniel. AU - Horm, Teresa. AU - George, Laeth. AU - Upchurch, Cameron. AU - Randall, Justin. AU - Weaver, Colby. AU - Sanford, Caitlin. AU - Miller, Austin. AU - Hernandez, Sebastian. AU - Dang, Hope. AU - Fares, Hanna. N1 - Publisher Copyright: © 2017 Gee et al.. PY - 2017. Y1 - 2017. N2 - Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. After fusing with late endosomes, lysosomes are reformed from the resulting hybrid organelles through a process that involves budding of a nascent lysosome, extension of the nascent lysosome from the hybrid organelle, while ...
Semantic Scholar extracted view of Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. by Annika Brun et al.
Diril, M. K., Schmidt, S., Krauß, M., Gawlik, V., Joost, H.-G., Schürmann, A., Haucke, V. and Augustin, R. (2009), Lysosomal localization of GLUT8 in the testis - the EXXXLL motif of GLUT8 is sufficient for its intracellular sorting via AP1- and AP2-mediated interaction. The FEBS Journal, 276: 3729-3743. doi: 10.1111/j.1742-4658.2009.07089.x ...
View Notes - Lecture 13 11 from BICD 110 at UCSD. Lecture 13 11/02/07 Golgi Structure/Function, Lysosome, Exocytosis Glycosylation Protects lysosome membrane proteins from autodegradation
Recent data both from cell-free experiments and from cultured cells have shown that lysosomes can fuse directly with late endosomes to form a hybrid organelle. This has a led to a hypothesis that dense core lysosomes are in essence storage granules for acid hydrolases and that, when the former fuse with late endosomes, a hybrid organelle for digestion of endocytosed macromolecules is created. Lysosomes are then re-formed from hybrid organelles by a process involving condensation of contents. In this Commentary we review the evidence for formation of the hybrid organelles and discuss the current status of our understanding of the mechanisms of fusion and lysosome re-formation. We also review lysosome biosynthesis, showing how recent studies of lysosome-like organelles including the yeast vacuole, Drosophila eye pigment granules and mammalian secretory lysosomes have identified novel proteins involved in this process. ...
Lysosomes degrade and recycle transported cellular components and internalized material by fusing with autophagosomes, phagosomes, and late endosomes. The resulting lysosomal breakdown products are used to generate new macromolecules and to provide energy in response to the nutritional needs of the cell. Recently, lysosome functions were expanded to include roles in nutrient sensing and energy metabolism (4). In this study, we report that the exposure of macrophages to LPS or heat-killed bacteria raises AGS3 levels. The increases in AGS3 reduced signaling through the mTOR pathway. However, in a nutrient-replete state this did not lead to a substantive increase in autophagy, but it did facilitate the nuclear translocation of TFEB, which transcriptionally activates many of the genes involved in lysosomal biogenesis and function. The subsequent increase in lysosomal biogenesis/function helped macrophages to resist intracellular infections by several strains of antibiotic-resistant ...
In many cases, apoptosis may be initiated by a minor lysosomal destabilization, which some time later is followed by a secondary, more pronounced, lysosomal rupture. After exposure to low concentrations of sphingosine, a lysosomotropic detergent, Jurkat and J774 cells underwenr apoptotic cell death, while cells exposed to higher concentrations of this agent showed necrosis. Sphingosine-induced apoptosis was partly prevented by the inhibitors of lysosomal aspartic or cysteine proteases, pepstatin A or E64d. Under these conditions, caspase-3 like activity was reduced 40-55%, suggesting that lysosomal enzymes could be upstream activators of caspase-3.. In J774 cells over-expressing Bcl-2, the early oxidant-induced lysosomal destabilization takes place, but the delayed secondary lysosomal rupture and ensuing apoptosis are both suppressed. Phosphorylation of Bcl-2 seems to be required for this anti-apoptotic effect because the protection is amplified by pre-treatment with phorbol 12-myristate ...
Lysosomes are one of the major degradative organelles in eukaryotic cells that carry out diverse cellular functions. Lysosomes show highly dynamic behaviors, including homotypic and heterotypic fusions, fission, and formation/reformation, which itself involves budding, extension, and scission. We carried out an unbiased forward mutational screen to identify novel regulators of lysosome dynamics and/or function; this screen is based on the degradation of a substrate, GFP, that is endocytosed by scavenger cells in worms. We identified cup-5 and six additional proteins that have lysosomal functions in C. elegans coelomocytes. CUP-16 is only conserved in the genus Caenorhabditis, and likely functions in endocytic uptake at the plasma membrane and in lysosomal degradation. Besides CUP-16, five of the mammalian homologs of the other CUP proteins, CIC-7, OSTM1, PLEKHM1, Cystinosin, and TRPML1, had been previously implicated in lysosome biology, thus validating this approach (Bach 2001; Lange et al. ...
The mechanisms involved in radiation-induced cellular injury and death remain incompletely understood. In addition to the direct formation of highly reactive hydroxyl radicals (HO.) by radiolysis of water, oxidative stress events in the cytoplasm due to formation of H2O2 may also be important. Since the major pool of low-mass redox-active intracellular iron seems to reside within lysosomes, arising from the continuous intralysosomal autophagocytotic degradation of ferruginous materials, formation of H2O2 inside and outside these organelles may cause lysosomal labilization with release to the cytosol of lytic enzymes and low-mass iron. If of limited magnitude, such release may induce reparative autophagocytosis, causing additional accumulation of redox-active iron within the lysosomal compartment. We have used radio-resistant histiocytic lymphoma (J774) cells to assess the importance of intralysosomal iron and lysosomal rupture in radiation-induced cellular injury. We found that a 40 Gy ...
The exact mechanism by which the atherogenic lipids oxLDL and CC perturb lysosomal function is not known. Oxidized LDL is taken up by macrophage scavenger receptors and is trafficked to the endolysosomal compartment. Oxidized LDL can then bind and inactivate cathepsins with high affinity,30 inactivate other proteases including the Naβ Gases,31 and produce a form of apolipoproteinB that is highly resistant to hydrolysis.32,33 OxLDL has also been demonstrated in endothelial and smooth muscle cells to inhibit activity and expression of the enzyme crucial to cholesterol ester hydrolysis, LIPA.34 Most recently, the formation of cholesterol microcrystals and ensuing disruption of lysosomal integrity has directly been linked to the buildup of oxLDL in the lysosomal compartment.14 Such a mechanism would favor the notion that the mechanism of lysosomal dysfunction mediated by oxLDL and larger CC lies in a continuum (with the oxLDL pool eventually precipitating as insoluble crystals). Our data support ...
TY - JOUR. T1 - FIG4 regulates lysosome membrane homeostasis independent of phosphatase function. AU - Bharadwaj, Rajnish. AU - Cunningham, Kathleen M.. AU - Zhang, Ke. AU - Lloyd, Thomas E.. N1 - Funding Information: The MPI Imaging Core is funded by an NINDS Core Center Grant (P30 NS050274: JHU Center for Neuroscience Research). This work was supported by an NIH/NINDS R01NS082563 to T.E.L. and an ALSA fellowship to K.Z.. PY - 2016. Y1 - 2016. N2 - FIG4 is a phosphoinositide phosphatase that is mutated in several diseases including Charcot-Marie-Tooth Disease 4J (CMT4J) and Yunis-Varon syndrome (YVS). To investigate the mechanism of disease pathogenesis, we generated Drosophila models of FIG4-related diseases. Fig4 null mutant animals are viable but exhibit marked enlargement of the lysosomal compartment in muscle cells and neurons, accompanied by an age-related decline in flight ability. Transgenic animals expressing Drosophila Fig4 missense mutations corresponding to human pathogenic ...
One contributing factor to the increased ability of more stable antigens to elicit immune responses is that the restricted susceptibility to lysosomal proteolysis favored the production of peptide-MHC class II complexes by DCs, at least in vitro (Fig. 2 E and Fig. 4 D). In addition, and just as important in an in vivo setting, we found that the increased stability to lysosomal proteolysis also favored the retention of antigens captured by DCs to lymphoid organs. 16 h after a single intradermal injection, the stable forms of RNase (Alexa 488-RNase-A) could be detected in CD11c+ DCs in the draining lymph nodes (Fig. 1 D). In contrast, the rapidly degraded form (Alexa 647-RNase-S) was barely detectable under the same conditions (Fig. 1 D). Combined with the fact that differential immunogenicity was observed by adoptively transferring DCs containing either RNase-A or RNase-S (Fig. 2 D), these results strongly suggest that at least one effect of decreased susceptibility to proteolysis is to ...
article{9e6ef65e-280f-480c-95c2-8ec585bac8f7, abstract = {Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. cDNAs for both soluble and transmembrane (tm) proteins were expressed in the human YT-Indy NK-cell line. Targeting of a soluble TNF receptor (sTNFR1) was achieved by expressing a cDNA construct with a transmembrane sequence to facilitate ER-export and by incorporating a cytosolic sorting signal (Y) from CD63 to overcome constitutive secretion. The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with subcellular fractionation, immunoelectron microscopy, and immunofluorescence microscopy. A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. Expression of ...
The Pryor lab is a cell biology group that is interested in the biogenesis of lysosomes and phagolysosomes, the role of lysosomes in disease and additionally how lysosomes are manipulated by intracellular pathogens.. 1. Lysosome Biogenesis. The lysosome was traditionally regarded as a dead-end hydrolytic organelle for the recycling of waste products. However, in recent years our understanding of the lysosome has changed and it is now clear that the lysosome is a signalling hub and is crucial for cellular homeostasis. Lysosome dysfunction can lead to diseases such as cancer, neurodegeneration and obesity. One overarching theme to our research are the molecules involved in regulating lysosome function. Projects are currently investigating chaperone mediated autophagy and lysosome biogenesis by transcription factors.. ...
Villamil Giraldo AM, Fyrner T, Wennmalm S, Parikh AN, Öllinger K, Ederth T Langmuir 32 (50) 13566-13575 [2016-12-20; online 2016-12-13] Lysosomotropic detergents (LDs) selectively rupture lysosomal membranes through mechanisms that have yet to be characterized. A consensus view, currently, holds that LDs, which are weakly basic, diffuse across cellular membranes as monomers in an uncharged state, and via protonation in the acidic lysosomal compartment, they become trapped, accumulate, and subsequently solubilize the membrane and induce lysosomal membrane permeabilization. Here we demonstrate that the lysosomotropic detergent O-methyl-serine dodecylamide hydrochloride (MSDH) spontaneously assembles into vesicles at, and above, cytosolic pH, and that the vesicles disassemble as the pH reaches 6.4 or lower. The aggregation commences at concentrations below the range of those used in cell studies. Assembly and disassembly of the vesicles was studied via dynamic light scattering, zeta potential ...
The lack or complexity of high resolution technologies and the need for labelled compound derivatives represents a major limitation on the study of intracellular distribution dynamics of pharmacological agents. The intrinsic, label-free and organelle-specific fluorescence activity of nintedanib presented in this study provides a powerful tool to dissect intracellular accumulation and distribution dynamics of this clinically approved small molecule TKI. The observation that lysosomal alkalization via V-ATPase inhibition sensitized lung cancer cells towards nintedanib suggests that protonation-based lysosomal sequestration represents a cell-intrinsic protection mechanism against this FGFR inhibitor. In accordance, various chemotherapeutic agents including doxorubicin, mitoxantrone and vincristine but also TKIs such as gefitinib, lapatinib and sunitinib have been reported to be subject to inactivating lysosomal sequestration [23, 30]. Together, these findings support a yet underestimated central ...
n animal regeneration, control of position-dependent cell proliferation is crucial for the complete restoration of patterned appendages in terms of both, shape and size. However, detailed mechanisms of this process are largely unknown. In this study, we identified leucine/glutamine and v-ATPase/lysosomal acidification, via mechanistic target of rapamycin complex 1 (mTORC1) activation, as effectors of amputation plane-dependent zebrafish caudal fin regeneration. mTORC1 activation, which functions in cell proliferation, was regulated by lysosomal acidification possibly via v-ATPase activity at 3 h post amputation (hpa). Inhibition of lysosomal acidification resulted in reduced growth factor-related gene expression and suppression of blastema formation at 24 and 48 hpa, respectively. Along the proximal-distal axis, position-dependent lysosomal acidification and mTORC1 activation were observed from 3 hpa. We also report that Slc7a5 (L-type amino acid transporter), whose gene expression is ...
EIPA-modulated retrograde movement of lysosomes depended on the activity of Rab7, a GTPase known to traffic late endosomes and lysosomes towards the nucleus (Johansson et al., 2007) and the Rab7 effector RILP, which is similar to the mechanism of Troglitazone-induced retrograde lysosome trafficking (Steffan and Cardelli, 2010). In fact, lysosomes in Rab7-KD- and DN-RILP-expressing cells were more peripherally located than in vector control cells. Also, HGF-induced invasion by Rab7-KD cells was not blocked by EIPA, in contrast to control cells. Finally, Fig. 6 demonstrates that Rab7-KD cells were more invasive and secreted more cathepsin B than control cells in the absence of HGF. We conclude that a more peripheral cellular location of lysosomes may be important in regulating invasion, and that EIPA blocks invasion by stimulating retrograde lysosome transport or preventing anterograde movement.. In support of this idea, overexpression of WT-RILP induced lysosome aggregation near the nucleus and ...
We have followed the transfer of EGF-EGF receptor (EGFR) complexes from endosomal vacuoles that contain transferrin receptors (TfR) to lysosome vacuoles identified by their content of HRP loaded as a 15-min pulse 4 h previously. We show that the HRP-loaded lysosomes are lysosomal-associated membrane protein-1 (LAMP-1) positive, mannose-6-phosphate receptor (M6PR) negative. and contain active acid hydrolase. EGF-EGFR complexes are delivered to these lysosomes intact and are then rapidly degraded. Preactivating the HRP contained within the preloaded lysosomes inhibits the delivery of EGFR and degradation of EGF, and results in the accumulation of EGFR-containing multivesicular bodies (MVB). With time these accumulating MVB undergo a series of maturation changes that include the loss of TfR, the continued recruitment of EGFR, and the accumulation of internal vesicles, but they remain LAMP-1 and M6PR negative. The mature MVB are often seen to make direct contact with lysosomes containing ...
Cellular clearance is a fundamental process required by the cells of every species. In eukaryotes, most of the cellular clearing processes occur in a specialized organelle, the lysosome. Given that the requirements of the degradative machinery in a cell may vary depending on tissue type, age and environmental conditions, we postulated that a system coordinates lysosomal activity and that lysosomal function is subject to transcriptional regulation. Using a systems biology-based approach, we discovered a gene regulatory network (CLEAR: Coordinated Lysosomal Enhancement And Regulation) that controls lysosomal biogenesis and function (Sardiello et al, Science 2009) and a master gene, the bHLH-leucine zipper transcription factor TFEB, which binds to CLEAR target sites in the promoter of lysosomal genes and positively regulates their expression (Sardiello et al, Science 2009). TFEB overexpression induces lysosomal biogenesis and increases the cells ability to degrade complex molecules such as mutated ...
Settembre C., Zoncu R., Medina D.L., Vetrini F., Erdin S., Erdin S., Huynh T., Ferron M., Karsenty G., Vellard M.C., Facchinetti V., Sabatini D.M., Ballabio A.. The lysosome plays a key role in cellular homeostasis by controlling both cellular clearance and energy production to respond to environmental cues. However, the mechanisms mediating lysosomal adaptation are largely unknown. Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane. When nutrients are present, phosphorylation of TFEB by mTORC1 inhibits TFEB activity. Conversely, pharmacological inhibition of mTORC1, as well as starvation and lysosomal disruption, activates TFEB by promoting its nuclear translocation. In addition, the transcriptional response of lysosomal and autophagic genes to either lysosomal dysfunction or pharmacological inhibition of mTORC1 is suppressed in TFEB-/-cells. Interestingly, ...
The lysosomal acidification defect linked to cytotoxicity of mutations in the P-type ATPase ATP13A2/PARK9 in Parkinsons disease (PD) prompts comparison to the similar mechanism operating in AD due to mutations of presenilin 1. Dehay and colleagues used nearly the same extensive battery of methods as Lee et al. (2010) to evaluate autophagy and lysosomal function in fibroblasts from PD patients and other model cell systems. While the two studies implicate different lysosomal constituents in these two diseases, they reveal pathogenic mechanisms involving defects in lysosome function that are remarkably similar and mutually validating. In both diseases, a lysosomal component needed for acidification is prematurely degraded in the endoplasmic reticulum and fails to reach the lysosome in amounts required for full function. In early onset AD caused by mutations of PS1, the V01a subunit of the proton pump vATPase is improperly chaperoned by the mutant PS1 and is degraded during its exit from the ER, ...
The CE moiety in Ox-LDL is hydrolyzed normally in lysosomes, but the resulting UC is trapped in the lysosomes secondary to the effect of oxysterols that are present in Ox-LDL.5 However, the mechanism responsible for trapping UC in the lysosomes has not been explored. Since SM binds UC with high affinity,18 19 20 21 22 the goal of this study was to examine whether SM accumulates in the macrophage lysosomes following cell incubation with Ox-LDL and whether SM accumulation can be responsible for trapping of the lipoprotein UC in the macrophage lysosomes. The present study indeed showed that Ox-LDL-derived SM accumulates in lysosomes as a result of an impaired SM hydrolysis by the lysosomal SMase. We also demonstrated that 7-KC, the major oxidized cholesterol derivative in Ox-LDL,5 40 41 is a potent inhibitor of macrophage lysosomal SMase. This oxysterol can thus lead to the lysosomal accumulation of Ox-LDL-derived UC secondary to SM accumulation in the macrophage lysosomes.. The mechanisms whereby ...
TY - JOUR. T1 - Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase. AU - Hamacher-Brady, Anne. AU - Choe, S. C.. AU - Krijnse-Locker, J.. AU - Brady, Nathan Ryan. PY - 2014/12/1. Y1 - 2014/12/1. N2 - Intrinsic apoptosis involves BH3-only protein activation of Bax/Bak-mediated mitochondrial outer membrane permeabilization (MOMP). Consequently, cytochrome c is released from the mitochondria to activate caspases, and Smac (second mitochondria-derived activator of caspases) to inhibit XIAP-mediated caspase suppression. Dysfunctional mitochondria can be targeted for lysosomal degradation via autophagy (mitophagy), or directly through mitochondria-derived vesicle transport. However, the extent of autophagy and lysosomal interactions with apoptotic mitochondria remains largely unknown. We describe here a novel pathway of endolysosomal processing of mitochondria, activated in response to canonical ...
The endolysosomal system and autophagy are essential components of macromolecular turnover in eukaryotic cells. The low-abundance signaling lipid PI(3,5)P2 is a key regulator of this pathway. Analysis of mouse models with defects in PI(3,5)P2 biosynthesis has revealed the unique dependence of the mammalian nervous system on this signaling pathway. This insight led to the discovery of the molecular basis for several human neurological disorders, including Charcot-Marie-Tooth disease and Yunis-Varon syndrome. Spontaneous mutants, conditional knockouts, transgenic lines, and gene-trap alleles of Fig4, Vac14, and Pikfyve (Fab1) in the mouse have provided novel information regarding the role of PI(3,5)P2in vivo. This review summarizes what has been learned from mouse models and highlights the utility of manipulating complex signaling pathways in vivo.
A cells digestive enzymes are enclosed in a membrane bound organelle. How can these molecules funtion in the cell? The KGB Agent answer: This membrane bound organelle is the lysosome that contains an array of enzymes capable of breaking down all types of biological polymers-proteins, nucleic acids, carbohydrates, and lipids. Lysosomes function as the digestive system of the cell, serving both to degrade material taken up from outside the cell and to digest obsolete components of the cell itself. In their simplest form, lysosomes are visualized as dense spherical vacuoles, but they can display considerable variation in size and shape as a result of differences in the materials that have been taken up for digestion. Lysosomes thus represent morphologically diverse organelles defined by the common function of degrading intracellular material. You will find lysosomes in nearly every animal-like eukaryotic cell. Lysosomes hold enzymes that were created by the cell. What creates a lysosome? Youll have
The rapid activation of the mechanistic target of rapamycin complex-1 (mTORC1) by growth factors is increased by extracellular amino acids through yet-undefined mechanisms of amino acid transfer into endolysosomes. Because the endocytic process of macropinocytosis concentrates extracellular solutes into endolysosomes and is increased in cells stimulated by growth factors or tumor-promoting phorbol esters, we analyzed its role in amino acid-dependent activation of mTORC1. Here, we show that growth factor-dependent activation of mTORC1 by amino acids, but not glucose, requires macropinocytosis. In murine bone marrow-derived macrophages and murine embryonic fibroblasts stimulated with their cognate growth factors or with phorbol myristate acetate, activation of mTORC1 required an Akt-independent vesicular pathway of amino acid delivery into endolysosomes, mediated by the actin cytoskeleton. Macropinocytosis delivered small, fluorescent fluid-phase solutes into endolysosomes sufficiently fast to ...
The cytotoxic activity of activated macrophages against tumorigenic target cells appears to be mediated by lysosomal enzymes of activated macrophage origin. Lysosomes of activated macrophages are secreted directly into the cytoplasm of susceptible target cells, which subsequently undergo heterolysis. This reaction can be inhibited by agents which prevent the exocytosis of macrophage lysosomes (hydrocortisone) or which interfere with the action of lysosomal enzymes (trypan blue). ...
TY - JOUR. T1 - The mannose 6-phosphate receptor and the biogenesis of lysosomes. AU - Griffiths, Gareth. AU - Hoflack, Bernard. AU - Simons, Kai. AU - Mellman, Ira. AU - Kornfeld, Stuart. PY - 1988/2/12. Y1 - 1988/2/12. N2 - Localization of the 215 kd mannose 6-phosphate receptor(MPR) was studied in normal rat kidney cells. Low levels of receptor were detected in the trans Golgi network, Golgi stack, plasma membrane, and peripheral endosomes. The bulk of the receptor was localized to an acidic, reticular-vesicular structure adjacent to the Golgi complex. The structure also labeled with antibodies to lysosomal enzymes and a lysosomal membrane glycoprotein (Igp120). While lysosome-like, this structure is not a typical lysosome that is devoid of MPRs. The endocytic marker α2macroglobulin-gold entered the structure at 37°C, but not at 20°C. With prolonged chase, most of the marker was transported from the structure into lysosomes. We propose that the MPR/Igp-enriched structure is a specialized ...
Although the pathogenesis of Parkinsons disease (PD) is considered multifactorial, evidence from genetics and cell biology has implicated specific molecular pathways. This article summarizes evidence that suggests that the level of intracellular alpha-synuclein is critical for the onset of neurodegeneration with Lewy bodies and dependent, to a large extent, on lysosomal degradation. The function of other key proteins that emerged from genetics is discussed: Pink1 and Parkin regulate the degradation of damaged mitochondria by the lysosome (mitophagy). Glucocerebrosidase and ATP13A2 are important components of this degradative organelle. VPS35 and LRRK2 may regulate trafficking within lysosome-dependent pathways, such as autophagy and endosomal vesicle recycling. Clinically, diffuse alpha-synucleinopathy or dementia seems to correlate with mutations which interfere with the broader function of lysosomal pathways, whereas a predominantly motor syndrome and nigrostriatal degeneration is associated with
The present experiments demonstrate that, just as for yeast cell-free homotypic vacuole fusion (Peters and Mayer 1998), cell-free heterotypic fusion of mammalian late endosomes and lysosomes requires Ca2+, probably mediating its effects via calmodulin. The Ca2+ is derived from the organelle lumen and is required at a late step in fusion after the requirement for a rab protein.. While the observation that BAPTA inhibits late endosome-lysosome membrane fusion with an IC50 of ∼2 mM, although EGTA has no effect even at 5 mM, is at first sight surprising, it is not without precedent in vertebrate membrane fusion systems. Thus, cell-free nuclear vesicle fusion during nuclear envelope assembly was shown to be inhibited by 5 mM BAPTA but unaffected by 12 mM EGTA (Sullivan et al. 1993). This effect was explained by the fact that at physiological pH, BAPTA exchanges Ca2+ ∼100 times faster than EGTA, reflecting faster rates of association and dissociation. Therefore, facilitated diffusion can cause ...
The CLEAR consensus sequence overlaps that of the E-box (CANNTG), a known target site for basic helix-loop-helix (bHLH) transcription factors (4). In particular, members of the microphthalmia-transcription factor E (MiT/TFE) subfamily of bHLH factors were found to bind sequences similar to the CLEAR consensus (5). The MiT/TFE subfamily is composed of four members in humans: MITF, TFE3, TFEB, and TFEC (6). To determine whether any of these proteins are able to modulate the expression of lysosomal genes, we transfected HeLa cells with plasmids carrying MITF, TFE3, TFEB, or TFEC cDNAs. We observed an increase in the mRNA levels of lysosomal genes (22 out of 23 genes tested) only after TFEB overexpression (Fig. 1C). Accordingly, we detected a significant increase in the activities of lysosomal enzymes β-glucosidase, Cathepsin D, and β-glucuronidase (fig. S5). Induction of lysosomal genes after TFEB overexpression was also observed in human embryonic kidney (HEK) 293 cells (fig. S6). We predicted ...
Lysosomes are small structures inside cells that specialize in breaking down unwanted proteins and other cellular components. These waste components could potentially damage or kill the cell. One biochemical process that lysosomes use to accomplish their task is called the autophagic-lysosomal pathway. Malfunction of lysosomes in general, and the autophagic-lysosomal pathway in particular, have been implicated in several neurodegenerative disorders, including Alzheimers disease. Impaired lysosomal function can lead to the overproduction of beta-amyloid from its parent molecule, amyloid precursor protein (APP). Beta-amyloid is a protein fragment closely linked to Alzheimers pathology. Recent studies have found that the production and activities of lysosomes are partly regulated by a transcription factor called TFEB. Transcription factors affect cellular activity by influencing how genes are expressed in the cells. In preliminary experiments, Abhinav Diwan, M.D., and colleagues have observed ...
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The microphthalmia family of transcription factors (MiT/TFEs) controls lysosomal biogenesis and is negatively regulated by the nutrient sensor mTORC1. However, the mechanisms by which cells with constitutive mTORC1 signaling maintain lysosomal catabolism remain to be elucidated. Using the murine epidermis as a model system, we found that epidermal Tsc1 deletion resulted in a phenotype characterized by wavy hair and curly whiskers, and was associated with increased EGFR and HER2 degradation. Unexpectedly, constitutive mTORC1 activation with Tsc1 loss increased lysosomal content via upregulated expression and activity of MiT/TFEs, whereas genetic deletion of Rheb or Rptor or prolonged pharmacologic mTORC1 inactivation had the reverse effect. This paradoxical increase in lysosomal biogenesis by mTORC1 was mediated by feedback inhibition of AKT, and a resulting suppression of AKT-induced MiT/TFE downregulation. Thus, inhibiting hyperactive AKT signaling in the context of mTORC1 loss-of-function ...
In metazoans, lysosomes are characterized by a unique tubular morphology, acidic pH, and specific membrane protein (LAMP) and lipid (cholesterol) composition as well as a soluble protein (hydrolases) composition. Here we show that perturbation to the eye-color gene, light, results in impaired lysosomal acidification, sterol accumulation, altered endosomal morphology as well as compromised lysosomal degradation. We find that Drosophila homologue of Vps41, Light, regulates the fusion of a specific subset of biosynthetic carriers containing characteristic endolysosomal membrane proteins, LAMP1, V0-ATPase and the cholesterol transport protein, NPC1, with the endolysosomal system, and is then required for the morphological progression of the multivesicular endosome. Inhibition of Light results in accumulation of biosynthetic transport intermediates that contain these membrane cargoes, whereas under similar conditions, endosomal delivery of soluble hydrolases, previously shown to be mediated by Dor, ...
Autophagy is of importance in the regulation of cell differentiation and senescence in podocytes, the highly differentiated glomerular epithelial cells. It is possible that derangement of autophagy under different pathological conditions activates or enhances Epithelial-to-Mesenchymal Transition (EMT) in podocytes, resulting in glomerular sclerosis. To test this hypothesis, the present study produced lysosome dysfunction by inhibition of vacuolar- type H+-ATPase (V-ATPase) to test whether deficiency of autophagic flux enhances EMT in podocytes. By Western blot analysis, inhibition of lysosome function by V-ATPase inhibitor or its siRNA was found to induce a significantly enhanced EMT in cultured podocytes, as shown by marked decreases in P-cadherin (P-cad) and zonula occludens-1 (ZO-1) as epithelial markers and simultaneous increases in the mesenchymal markers, fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA). These changes in EMT markers were confirmed by confocal microcopy.
Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis (PubMed:29019981). Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy. Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (PubMed:23993788, PubMed:27623384). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events. By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor
Exploring the mechanism of the drugs cancer-preventing action provided some intriguing insights.. At the doses used in the new study, which were similar to those needed to prevent malaria, chloroquine triggered the death of premalignant cells. This suggests that within the context of MYC overexpression, the drug induces apoptotic cell death-programmed cell death-in response to ineffective autophagic protein degradation and lysosomal changes in the cell. (Lysosomes are cellular recycling centers that degrade old and unwanted material in the cell and recycle building blocks that are used for cell growth.) The p53 protein can induce apoptosis in response to DNA damage or stress, and the studys results suggest that alterations in lysosomal function trigger a p53-dependent cell death response. Our studies have established that chloroquine inhibits a late step in the autophagy pathway by inhibiting lysosome functions that provide necessary material used to keep tumor cells alive under times of ...
By using video microscopy with fluorescent tagging of the two organelles, the scientists observed that the mitochondria and lysosomes formed stable contacts inside living human cells. The authors also employed other advanced imaging techniques - including electron microscopy and super-resolution imaging - to discover that the formation, and subsequent loosening, of these contacts is regulated by a lysosomal protein called RAB7.. The discovery of these mitochondria-lysosome contacts is extremely exciting, said first author Yvette Wong, PhD, a postdoctoral fellow in Kraincs laboratory. We now show that these contacts offer a potential site through which mitochondria and lysosomes can crosstalk, and it suggests that defects in the regulation of this contact site may drive the pathogenesis of various human diseases.. In follow-up studies, the scientists are now investigating how dysfunction of the proteins that tether mitochondria and lysosomes together may affect the function of the ...
In the cell, the proteasome and lysosomes represent the most important proteolytic machineries, responsible for the protein degradation in the ubiquitin-proteasome system (UPS) and autophagy, respectively. Both the UPS and autophagy are essential to protein quality and quantity control. Alterations …
TY - JOUR. T1 - Cationic lipids delay the transfer of plasmid DNA to lysosomes. AU - Wattiaux, R.. AU - Jadot, M.. AU - Laurent, N.. AU - Dubois, F.. AU - Wattiaux-De Coninck, Simone. N1 - Medline is the source for the MeSH terms of this document.. PY - 1996/10/14. Y1 - 1996/10/14. N2 - Plasmid S DNA, naked or associated with different cationic lipid preparations was injected to rats. Subcellular distribution of radioactivity in the liver one hour after injection, was established by centrifugation methods. Results show that at that time, S DNA has reached lysosomes. On the contrary, when S DNA was complexed with lipids, radioactivity remains located in organelles whose distribution after differential and isopycnic centrifugation, is clearly distinct from that of arylsulfatase, a lysosome marker enzyme. Injection of Triton WR 1339, a specific density perturbant of lysosomes, four days before S DNA injection causes a density decrease of radioactivity bearing structures, apparent one hour after ...
Synopsis: The realization of new technologies and the development of targeted biopharmaceutical therapies have accelerated in the last decade with over 30 such compounds currently in clinical trials. With ongoing development and evaluation of strategies, such as antibody drug conjugates, to effectively deliver compounds to targeted cell populations through the endocytic-lysosomal pathway, the development and availability of novel reagents will become paramount. Isolated rat hepatic tritosomes and human hepatic lysosomes are in vitro systems that can be utilized to quickly and conveniently evaluate compound stability and guide development direction of biopharmaceutical candidates. In this study, subcellular isolation techniques combined with immunoblotting, protease arrays, and enzymatic activity assays were carried out to characterize isolated rat tritosomes and human hepatic lysosomes ...
The lysosomes are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (where old or unneeded organelles or proteins, or microbes which have invaded the cytoplasm are delivered to the lysosome). Autophagy may also lead to autophagic cell death, a form of programmed self-destruction, or autolysis, of the cell, which means that the cell is digesting itself. Other functions include digesting foreign bacteria (or other forms of waste) that invade a cell and helping repair damage to the plasma membrane by serving as a membrane patch, sealing the wound. Lysosomes also do much of the cellular digestion required to digest tails of tadpoles and to remove the web from the fingers of a 3-6 month old fetus. This process of programmed cell death is called apoptosis.[1] ...
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The mechanisms by which altered processing, distribution and secretion of proteolytic enzymes occur, facilitating degradation of the extracellular matrix in invasive and metastatic cells, are not fully understood. Studies on the MCF-10 A breast epithelial cell line and its premalignant, c-Ha-ras-transfected MCF-10AneoT counterpart have shown that the ras-transfected cell line has a more alkaline pH. The objective of this study was to determine which organelles of the endosome-lysosome route were alkalinized and shifted to the cell periphery after ras-transfection. Antibodies to the hapten 2,4-dinitrophenyl (DNP), required for pH studies, were raised in rabbits and chickens using DNP-ovalbumin (DNP-OVA) as immunogen. Cationised DNP-OVA (DNP-catOVA) was also inoculated to increase antibody titres. Anti-hapten and carrier antibody titres were assessed. In rabbits, cationisation seems useful to increase anti-DNP titres if a non-self carrier protein (OVA) is used. In chickens, cationisation of ...
Endosomal-lysosomal pH defects are an emerging theme in mechanisms underlying a number of neurodegenerative diseases. To date, results from experiments in vivo and in vitro have revealed the importance of proper vesicular pH balance and optimal acidification in transporting and degrading cargo via the endocytic pathway [48, 49]. For instance, Lee et al. reported that, in presenilin1 (PSEN1)-deleted blastocysts, defective lysosome acidification was observed with a substaintially elevated lysosomal PH of 5.4 and PSEN1 is essential for the transport of mature V0a1 subunites of V-ATP to lysosomes for their acidification and proteolysis [50]. Specifically, dysregulation of acidification and intracellular pH perturbation could influence the activity of enzymes in endomembrane compartments, resulting in impaired clearance of protein aggregates downstream of elevated endomembrane system pH, or conversely, due to decreased cytoplasmic pH. Regarding the latter, asparaginyl endopeptidase (AEP) is a typical ...
TY - JOUR. T1 - Lysosomal dysfunction causes neurodegeneration in mucolipidosis II knock-in mice. AU - Kollmann, K.. AU - Damme, M.. AU - Markmann, S.. AU - Morelle, W.. AU - Schweizer, M.. AU - Hermans-Borgmeyer, I.. AU - Röchert, A. K.. AU - Pohl, S.. AU - Lübke, T.. AU - Michalski, J. C.. AU - Käkelä, R.. AU - Walkley, S. U.. AU - Braulke, T.. PY - 2012/9. Y1 - 2012/9. N2 - Mucolipidosis II is a neurometabolic lysosomal trafficking disorder of infancy caused by loss of mannose 6-phosphate targeting signals on lysosomal proteins, leading to lysosomal dysfunction and accumulation of non-degraded material. However, the identity of storage material and mechanisms of neurodegeneration in mucolipidosis II are unknown. We have generated knock-in mice with a common mucolipidosis II patient mutation that show growth retardation, progressive brain atrophy, skeletal abnormalities, elevated lysosomal enzyme activities in serum, lysosomal storage in fibroblasts and brain and premature death, ...
TY - JOUR. T1 - Eps8 is recruited to lysosomes and subjected to chaperone-mediated autophagy in cancer cells. AU - Welsch, Thilo. AU - Younsi, Alexander. AU - Disanza, Andrea. AU - Rodriguez, Jose Antonio. AU - Cuervo, Ana Maria. AU - Scita, Giorgio. AU - Schmidt, Jan. N1 - Funding Information: We would like to thank Sonja Bauer for her excellent technical assistance. This work was partly supported by the NIH Grant AG021904 (to AMC). PY - 2010/7. Y1 - 2010/7. N2 - Eps8 controls actin dynamics directly through its barbed end capping and actin-bundling activity, and indirectly by regulating Rac-activation when engaged into a trimeric complex with Eps8-Abi1-Sos1. Recently, Eps8 has been associated with promotion of various solid malignancies, but neither its mechanisms of action nor its regulation in cancer cells have been elucidated. Here, we report a novel association of Eps8 with the late endosomal/lysosomal compartment, which is independent from actin polymerization and specifically occurs in ...
Coat proteins appear to play a general role in intracellular protein trafficking by coordinating a membrane budding event with cargo selection. Here we show that the AP-2 adaptor, a clathrin-associated coat-protein complex that nucleates clathrin-coated vesicle formation at the cell surface, can also initiate the assembly of normal polyhedral clathrin coats on dense lysosomes under physiological conditions in vitro. Clathrin coat formation on lysosomes is temperature dependent, displays an absolute requirement for ATP, and occurs in both semi-intact cells and on purified lysosomes, suggesting that clathrin-coated vesicles might regulate retrograde membrane traffic out of the lysosomal compartment. ...
Chloroquine (CQ) or hydroxychloroquine [4]. The results suggest a labilizing effect of chloroquine …. A similar activation can be induced in the liver by glucagon treatment in vivo [l] or by amino acid. Levigate with a small amount of glycerin or distilled water. Jul 17, 2019 · Chloroquine is a lysosomal lumen alkalizer and a lysosomal autophagy inhibitor that impairs lysosomal functions. Chloroquine is. Chloroquine is a member of quinolone family and is a weak intercalating agent. As a result, cells are not able chloroquine lysosomal acidification to proceed with endocytosis, exosome release and phagolysosomal fusion in an orderly manner. D.-M. This accumulation leads to inhibition of lysosomal enzymes that require an acidic pH, and prevents fusion of endosomes and lysosomes 4. Chloroquine is a lysosomotropic agent that prevents endosomal acidification 1. CHQ has, however, since accrued a plethora of uses in the treatment and amelioration of several other diseases and conditions because of ...
Lysosomes and lysosomal enzymes play a central part in numerous cellular processes, including cellular nourishment, recycling, signaling, defense, and cell death. demonstrated by electron microscopy, with Rabbit polyclonal to STAT6.STAT6 transcription factor of the STAT family.Plays a central role in IL4-mediated biological responses.Induces the expression of BCL2L1/BCL-X(L), which is responsible for the anti-apoptotic activity of IL4. an electron dense appearance and membranous whorls [1, 7, 8]. Lysosomes consist of a phospholipid bilayer membrane enclosing a lumen wherein the pH is definitely managed at 4.5C5.0 to facilitate the action of acid hydrolases (Number 1A) [9, 10]. In addition, the lysosomal membranes consist of integral proteins that are greatly glycosylated to prevent their personal degradation by the hydrolytic enzymes in the lumen. The major proteins, lysosome-associated membrane proteins LAMP-1, LAMP-2, LAMP-3 or tetraspanin CD63, and lysosome integral membrane protein LIMP-2, ...
Two murine lysosome-associated membrane proteins, LAMP-1 of 105,000-115,000 D and LAMP-2 of 100,000-110,000 D, have been identified by monoclonal antibodies that bind specifically to lysosomal membranes. Both glycoproteins were distinguished as integral membrane components solubilized by detergent solutions but not by various chaotropic agents. The lysosome localization was demonstrated by indirect immunofluorescent staining, co-localization of the antigen to sites of acridine orange uptake, and immunoelectron microscopy. Antibody binding was predominantly located at the limiting lysosomal membrane, distinctly separated from colloidal gold-labeled alpha-2-macroglobulin accumulated in the lumen during prolonged incubation. LAMP-1 and LAMP-2 also appeared to be present in low concentrations on Golgi trans-elements but were not detected in receptosomes marked by the presence of newly endocytosed alpha-2-macroglobulin, or in other cellular structures. LAMP-1 and LAMP-2 were distinguished as ...
Background Mutations in αB-crystallin result in proteotoxic cardiomyopathy with desmin mislocalization to protein aggregates. Intermittent fasting ( IF ) is a novel approach to activate transcription factor EB (TFEB), a master regulator of the autophagy-lysosomal pathway, in the myocardium. We teste …
Pharmacological challenges to oncogenic Ras-expressing cancer cells have shown a novel type of cell death, ferroptosis, which requires intracellular iron. In the present study, we assessed ferroptosis following treatment of human fibrosarcoma HT1080 cells with several inhibitors of lysosomal activity and found that they prevented cell death induced by the ferroptosis-inducing compounds erastin and RSL3. Fluorescent analyses with a reactive oxygen species (ROS) sensor revealed constitutive generation of ROS in lysosomes, and treatment with lysosome inhibitors decreased both lysosomal ROS and a ferroptotic cell-death-associated ROS burst. These inhibitors partially prevented intracellular iron provision by attenuating intracellular transport of transferrin or autophagic degradation of ferritin. Furthermore, analyses with a fluorescent sensor that detects oxidative changes in cell membranes revealed that formation of lipid ROS in perinuclear compartments probably represented an early event in ...
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Abstract: Effects of single and repeated injections of lysosomotropic agent chloroquine on lysosomal proteolytic activity and physico-chemical properties of rat liver lysosomes have been studied. Chloroquine was administered intraperitoneally to rats at a dose of 30 mg/kg of body mass. Osmotic properties, lysosomal enzymes activity and functional state of the system of mononuclear phagocytes were estimated. No alterations of colloid carbon clearance followed by a single dose of chloroquine administration were noted. Distinct alterations in osmotic properties, weak labilization of lysosomes and an increase in acid hydrolases activity were similar after single and/or repeated chloroquine administrations, whereas activation of cysteine proteinases and cathepsin D were most pronounced. Chloroquine accumulation by rat liver cells proved to be similar, but the drug excretion was longer after repeated injections. The lysosomal disorders noted were similar to those symptoms of lysosomal storage disease ...
Cellular organelles enable the spatial clustering of molecules, thus favoring their interactions in microenvironments ideally suited for specific complex functions. A well‐known function of the lysosome is to degrade and recycle cellular waste. Extracellular materials reach the lysosome mainly through endocytosis and phagocytosis, while a completely different process, autophagy, mediates the delivery of intracellular materials. Autophagy is activated by a broad range of cellular stress‐inducing conditions and mediates the degradation of protein aggregates, oxidized lipids, damaged organelles, and intracellular pathogens. The process typically involves the formation of double membrane‐bound vesicles, the autophagosomes, which sequester cytoplasmic material and then fuse with lysosomes. Materials that reach the lysosome are degraded by lysosomal hydrolases, and the resulting breakdown products are used to generate new cellular components and energy in response to the nutritional needs of the ...
The cDNA sequence of mouse LAMP 2: evidence for two classes of lysosomal membrane glycoproteins is an eagle-i resource of type Journal article at eagle-i Network Shared Resource Repository.
TY - JOUR. T1 - The kinetics of phagosome maturation as a function of phagosome/lysosome fusion and acquisition of hydrolytic activity. AU - Yates, Robin M.. AU - Hermetter, Albin. AU - Russell, David G.. PY - 2005. Y1 - 2005. U2 - 10.1111/j.1600-0854.2005.00284.x. DO - 10.1111/j.1600-0854.2005.00284.x. M3 - Article. VL - 6. SP - 413. EP - 420. JO - Traffic. JF - Traffic. SN - 1398-9219. IS - 5. ER - ...
A lysosome is a cell organelle.[1] They are like spheres. They have hydrolytic enzymes which can break down almost all kinds of biomolecules, including proteins, nucleic acids, carbohydrates, lipids, and cellular debris. They contain more than 50 different enzymes. By convention, lysosome is the term used for animal cells.[2] In plant cells, vacuoles do similar functions. With a wider definition, lysosomes are found in the cytoplasm of plant and protists as well as animal cell. Lysosomes work like the digestive system to break down, or digest, proteins, acids, carbohydrates, dead organelles, and other unwanted materials.[3] They break up larger molecules into smaller molecules. Those smaller molecules can then be used again as building blocks for other large molecules.[3] ...
Lysosomes are membrane-delimited organelles in animal cells serving as the cells main digestive compartment to which all sorts of macromolecules are delivered for degradation. They contain more than 40 hydrolases in an acidic environment (pH of about 5). After synthesis in the ER, lysosomal enzymes are decorated with mannose-6-phosphate residues, which are recognized by mannose-6-phosphate receptors in the trans-Golgi network. They are packaged into clathrin-coated vesicles and are transported to late endosomes. Substances for digestion are acquired by the lysosomes via a series of processes including endocytosis, phagocytosis, and autophagy ...
Niemann-Picks disease type C1 is a rare, inheritable and currently untreatable lysosomal storage disease. The main characteristic of this disease is accumulation of cholesterol in the endo-lysosomal system. The cause of the disease is a mutation in the NPC1 protein, which is necessary for egress of cholesterol from lysosomes. The disease is severe and progressive and includes neurological symptoms such as ataxia, dysphagia and dementia. In most cases, (hepato)splenomegaly is also present. Besides, Niemann-Picks disease type C is simmilar to Alzheimers disease. Neurofibrillary tangles and amyloidogenic processing of APP are present in both of these conditions. An effort was made to see this disease in a new light by investigating the N-glycans of lysosomal membrane glycoproteins. CHO-NPC1 -/- cell culture was used for this purpose, as well as CHOwt cells as a control group. In order to isolate the lysosomal membrane glycoproteins, magnetic chromatography and Triton x-114 mediated phase ...
Autophagy (Autofagia) Mohamed Elgendy MD, PhD Autophagy (Autofagia) Mohamed Elgendy MD, PhD [email protected] Auto+phagy Greek for Self Eating Autophagy = Recycling Types of Autophagy • 1-Macro-autophagy • 2-Micro-autophagy • 3-Chaperon-mediated autophagy Macro-autophagy 1-Induction Lysosome Autophagosome Fusion LC 3 LC3 II PE LC 3 LC 3 Phagophore 2-Nucleation Autolysosome LC3 I 3-Maturation Other types of Autophagy • Macro-autophagy Delivery of cytoplasmic cargo to the lysosome through the intermediary of a double membranebound vesicle, referred to as an autophagosome, that fuses with the lysosome to form an autolysosome. • Micro-autophagy Cytosolic components are directly taken up by the lysosome itself through invagination of the lysosomal membrane • Chaperon-mediated autophagy Targeted proteins are translocated across the lysosomal membrane in a complex with chaperone proteins (such as Hsc-70) that are recognized by the lysosomal membrane receptor LAMP-2A, resulting in their ...
EMBO Workshop: Lysosomes and metabolism (http://meetings.embo.org/event/18-lysosomes) For many years, the lysosome or vacuole represented the cells waste-yard, where cargo delivered through autophagy pathways and from the late endosome is digested or recycled. However, compelling recent evidence suggests that the lysosome harbors a complex nutrient sensing machinery that regulates important cellular processes including autophagy, lysosomal biogenesis, … Continue reading EMBO Workshop: Lysosomes and Metabolism. ...
We tested the hypothesis that TAG accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally linked with the onset of hepatic insulin resistance. We found that LIPA could be translocated between qualitatively different depots (light and dense lysosomes). In contrast to dense lysosomal fraction, LIPA associated with light lysosomes exhibits high activity on both intracellular TAG and exogenous substrate and prandial- or diet-dependent regulation. On standard diet, LIPA activity was upregulated in fasted and downregulated in fed animals. In the HFD group, we demonstrated an increased TAG content, elevated LIPA activity, enhanced production of diacylglycerol, and the abolishment of prandial-dependent LIPA regulation in light lysosomal fraction. The impairment of insulin signalling and increased activation of PKC|i|ε|/i| was found in liver of HFD-fed animals. Lipolysis
Lysosomal Lipid Binding and Transfer Proteins. Sphingolipid Metabolism, Intervesicular Lipid Transfer and Vesicle Fusion Fig. 1: Proposed topology of endocytosis and lysosomal degradation.
Autophagy is considered primarily a cell survival process, although it can also lead to cell death. However, the factors that dictate the shift between these 2 opposite outcomes remain largely unknown. In this work, we used D9 -tetrahydrocannabinol (THC, the main active component of marijuana, a compound that triggers autophagy-mediated cancer cell death) and nutrient deprivation (an autophagic stimulus that triggers cytoprotective autophagy) to investigate the precise molecular mechanisms responsible for the activation of cytotoxic autophagy in cancer cells. By using a wide array of experimental approaches we show that THC (but not nutrient deprivation) increases the dihydroceramide:ceramide ratio in the endoplasmic reticulum of glioma cells, and this alteration is directed to autophagosomes and autolysosomes to promote lysosomal membrane permeabilization, cathepsin release and the subsequent activation of apoptotic cell death. These findings pave the way to clarify the regulatory mechanisms ...
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. Lysosomal Ca2+ Signaling Regulates High Glucose-Mediated Interleukin-1β Secretion via Transcription Factor EB in Human Monocytic Cells.
We study the retinal pigment epithelium (RPE), which nourishes and supports the light-sensingphotoreceptors in the retina. The RPE is also the initial site of damage in macular degenerations. How RPE injury leads to vision loss is not yet clear. We use cutting-edge live imaging of healthy and diseased retina along with animal models and advanced cellular and molecular assays to identify early insults that compromise RPE function and can eventually lead to AMD. To gain insight into disease pathogenesis, our research team investigates mechanisms that regulate critical pathways such as autophagy and lysosome function, mitochondrial dynamics, complement-mediated inflammation, and RPE-photoreceptor communication.. ...
Mouse beta-glucuronidase has a dual intracellular localization, being present in both endoplasmic reticulum and lysosomes of several tissues. Previous studies demonstrated that the protein egasyn is complexed with microsomal but not lysosomal glucuronidase and that a mutant lacking egasyn is deficient in microsomal, but not lysosomal, glucuronidase. By means of a recently developed radioimmunoassay for egasyn, the relationship between microsomal glucuronidase levels and egasyn levels has been examined in various adult tissues, during postnatal development in liver, and after androgen induction of glucuronidase in kidney. The results indicate that the relative availability of egasyn determines the balance between glucuronidase incorporation into membranes and that into lysosomes.
Body proteins in cats were prelabelled with [14C]valine, and protein degradation was studied in isolated hepatocytes. Amino acids appeared to have a direct inhibitory effect on protein degradation, but the effects were generally smaller than those previously shown in the rat. The amino acid control of protein degradation in the cat differs from that in the rat, as shown by the lack of effects of glutamine, asparagine, arginine or methionine in cat hepatocytes. This may be related to the unique features of protein metabolism of this species. NH4Cl, leupeptin and amino acids, which suppress lysosomal protein degradation by different mechanisms, caused less than 30% inhibition of protein degradation when used at the optimum concentrations reported for the rat. The ability of the lysosomal system to respond to nutritional deprivation is apparently lower in the cat than in the rat.. ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the beta subunit of lysosomal acid phosphatase (LAP). LAP is chemically and genetically distinct from red cell acid phosphatase. The encoded protein belongs to a family of distinct isoenzymes which hydrolyze orthophosphoric monoesters to alcohol and phosphate. LAP-deficiencies in mice cause multiple defects including bone structure alterations, lysosomal storage defects in the kidneys and central nervous system, and an increased tendency towards seizures. An enzymatically-inactive allele of LAP in mice exhibited a more severe phenotype than the null allele, and defects included cerebellum abnormalities, growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014 ...
Lysosomes are cells recycling and waste disposal system. It contains a battery of enzymes (acid hydrolases) that degrade a wide variety of macromolecules and cellular debris into reusable forms. In so doing lysosomes play a vital role in maintaining cellular homeostasis. The broad goal of our research is to understand the role of this fascinating organelle in human health and diseases. We use various methods ranging from molecular biology, cell biology, protein biochemistry to genomic and proteomic tools to address our research problems. Current research in our laboratory is focused on two major areas: 1. To investigate the pathogenesis of mucopolysaccharidoses, a group of genetic disorders caused by deficiency of one of the eleven lysosomal enzymes required for stepwise degradation of glycosaminoglycans (GAGs). Widespread lysosomal accumulation of undegraded or partially degraded GAGs results in cellular and multiple organ dysfunctions leading to premature death in most cases. The genetic ...
Key Difference - Lysosome vs Vacuole Lysosome is a membrane bound organelle designed for the functions of digestion and phagocytosis. Vacuole is another
Two closely related human Arls, Arl8a and Arl8b, were found to localise to lysosomes in mammalian cells. conventionally, membrane binding of Arf and Arl proteins is mediated by both an N-terminal myristoyl group and an N-terminal amphipathic helix that are inserted into the lipid bilayer upon activation of the GTPase. Arl8 GPTases lack myristolylation sites, and examination of the N-terminus of Arl8b revealed that it contains an acetyl group instead, and this acetylated methionine is necessary for its lysosomal location. Lysosomes of cells overexpressing Arl8b move more frequently, suggesting a role for Arl8a and Arl8b as positive regulators of lysosomal transport. Arl4a, Arl4c and Arl4d are very similar in sequence and were found to act in a pathway upstream of Arf6, Arf6 is a regulator of key processes at the plasma membrane, such as endocytosis, actin dynamics and cell adhesion. One of the major activators of Arf6 is the exchange factor ARNO (Arf nucleotide binding site opener). In order to ...
NPC2, a secreted protein containing a lipid recognition domain, may function in regulating the transport of cholesterol through the late endosomal/lysosomal system. NPC2 may be involved in the regulation of the lipid composition of sperm membranes during the maturation in the epididymis. Mutations in this gene have been associated with Niemann-Pick disease, type C2 and frontal lobe atrophy.
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The macrophage-stimulating effect of Turkey Tail mushroom extracted from Coriolus versicolor (Turkey Tail mushroom) was investigated, and their effectiveness was compared with that of lipopolysaccharide (LPS). The purified polysaccharide (CV-S2-Fr.I) of C. versicolor obtained by Sepharose CL-6B gel chromatography stimulated macrophage lysosomal enzyme activity by 250% at a concentration of 100 microg/mL, which was higher than that of LPS at the same concentration. When CV-S2-Fr.I was used in combination with interferon-gamma, there was a marked cooperative induction of nitric oxide production. However, CV-S2-Fr.I had no effect on nitric oxide production by itself. The proportion of C3-positive macrophages in the CV-S2-Fr.I group increased by 7.2-fold compared with the control group.. ...
In order to further investigate and compare the degree of co-localization of DOX to different subcellular compartments, several parameters were calculated including Pearsons coefficient (P), the overlap coefficient (O), and Manders coefficients M1 and M2.72 M1 reflects the portion of cellular components that co-localize with DOX, and M2 indicates the portion of DOX co-localized with cellular components. All of these coefficients were converted into a heat map (Fig. 5B) in which high values of P, O, and M1 are considered to be indicative of high co-localization while M2 is not. According to the heat map, high values of P, O, and M1 were found in the nuclei, lysosomes, and mitochondria indicating high levels of DOX distribution to these compartments. Lysosomes had the highest degree of co-localization to DOX, which was expected because lysosomes can entrap most exogenous substances, including drugs and smaller nanocarriers.24,25 It is commonly assumed that histidine/histamine functional NPs44,45 ...
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For other Linux-based storre or web servers, youll have to adjust accordingly. To evaluate lysosomal morphology, cells were stained with 500 nm Lysotracker Red (Invitrogen) for 30 min. Esrver addressing bboot VPS plans. S4 ). 2 NP-40), and lysed by lysozyme treatment (1. There are no specific FAQs related to this product. Configuratio, make it executable by running chmod x Now, you can run restart windows server 2008 boot configuration data store to restart your server. Remember - if you maintain a copy, your JohnCompanies filesystem is your backup. I have also tried A Small Orangeв which gave me a bad experience. The player then conducts attacks against the other players PSFs. Shown in Windows server 2008 boot configuration data store 3 are median IgG responses to the VSP antigens from children by age ( Figure 3A ) and from the 30 Haitian adults ( Figure 3B ). Sinai West, holding an interest in the medicalsurgical treatment of Allergy, Asthma and Immunology. Not only that, but your website ...
Myotubularins phosphatase domain is a 3-phosphatases specific for membrane-embedded PtdIns3P and PtdIns(3,5)P2, two PIs that function within the endosomal-lysosomal ...
Its clear from the evidence, as well as common sense, that PPIs have a systemic effect on the entire body, not just the small function they are prescribed to adjust. PPIs launch an attack on basic cellular functioning, inhibiting healthy cell metabolism from taking place. When the bodys ability to convert the building blocks of life, namely proteins, carbohydrates, fats, and nucleic acids, into useable fuel is compromised, so is our immune system, and life begins shutting down. An older study that helped pioneer awareness of harm due to PPIs, is a 2013 study called Inhibition of lysosomal enzyme activities by proton pump inhibitors. Researchers observed that many of the adverse effects of PPIs are caused by systemically compromised immunity, a result of PPI inhibition of lysosomal enzymes. Lysosomes are essentially tiny membranes or sacs that carry enzymes essential to cellular metabolic functions. When PPIs inhibit this function, there is an increased incidence of tumors (tumorigenesis) and ...
The conserved oligomeric complex (COG) is a multi-subunit vesicle tethering complex that functions in retrograde trafficking at the Golgi. We have previously demonstrated that the formation of enlarged endo-lysosomal structures (EELSs) is one of the major glycosylation-independent phenotypes of cells depleted for individual COG complex subunits. Here, we characterize the EELSs in HEK293T cells using microscopy and biochemical approaches. Our analysis revealed that the EELSs are highly acidic and that vATPase-dependent acidification is essential for the maintenance of this enlarged compartment. The EELSs are accessible to both trans-Golgi enzymes and endocytic cargo. Moreover, the EELSs specifically accumulate endolysosomal proteins Lamp2, CD63, Rab7, Rab9, Rab39, Vamp7, and STX8 on their surface. The EELSs are distinct from lysosomes and do not accumulate active Cathepsin B. Retention using selective hooks (RUSH) experiments revealed that biosynthetic cargo mCherry-Lampl reaches the EELSs much ...
TY - JOUR. T1 - DRAM1 regulates autophagy flux through lysosomes.. AU - ZHANG, X. AU - QI, L. AU - WU, J. AU - QIN, Z. PY - 2013/6/1. Y1 - 2013/6/1. M3 - Article. C2 - 23696801. VL - 8(5): e63245.. JO - PLoS One.. JF - PLoS One.. ER - ...
XenoTech processes donor tissue every day. Our expertise and unique preparation procedures allow us to get the most out of each and every tissue. As a result, we often have surplus inventory of products remaining from our custom preparations, including Hepatocytes, Microsomes, S9, Cytosol, Homogenate, Lysosomes, Mast Cells, Mitochondria & Non-Parenchymal Cells from liver, kidney, intestine, lung, spleen, heart, muscle, eye, gland, brain and other tissue from cat, chicken, cow, dog, gerbil, goat, guinea pig, hamster, horse, human, minipigs, monkeys, mice, pig, rabbits, rats, sheep...
By studying the role of lysosomes in mitosis, an IDIBELL and UB group discovers that alterations in the separation of chromosomes cause a detectable nucleus morphology once mitosis has finished.
The main function of Golgi apparatus is secretion, packaging and modifying of the proteins. It is also involved in the synthesis of new membrane and lysosomes. ...
These gene mutations slow down the fusion between autophagic vacuoles and lysosomes, leading to the accumulation of autophagic ... Without the LAMP-2 protein, fusion between autophagic vacuoles and lysosomes occurs much slower, leading to the accumulation of ... Matzner U (2005). "Therapy of Lysosomal Storage Diseases". Lysosomes. Springer US. pp. 112-129. doi:10.1007/0-387-28957-7_10. ... which plays a role in the transport of cellular materials into the lysosome, mutations of the LAMP2 gene lead to little to no ...
Mutations of synuclein alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Within the lysosome/vacuole, the contents of the autophagosome are degraded via acidic lysosomal hydrolase. Microautophagy, on ... The autophagosome then travels through the cytoplasm of the cell to a lysosome in mammals, or vacuoles in yeast and plants, and ... In January 1962 they reported an increased number of lysosomes in rat liver cells after the addition of glucagon, and that some ...
In 1969 he gave the first clear-cut distinction between lysosomes and peroxisomes. In 1972, he and his wife discovered a new ... "It is largely due to Novikoff's bold and imaginative use of morphological techniques," de Duve praised him, "that lysosomes ... In 1955, now confident that the membranous particles were cell organelles, de Duve gave a hypothetical name "lysosomes" to ... In 1965 with de Duve, he confirmed the location of the hydrolytic enzymes of lysosomes. Novikoff further established the ...
... of lysosomes. Serendipity followed de Duve for another major discovery. After the confirmation of lysosome, de Duve's team was ... De Duve thought it was not a lysosome because it is not an acid hydrolase, typical of lysosomal enzymes; still, it had similar ... From insulin to lysosomes". Hormones. 5 (2): 151-5. doi:10.14310/horm.2002.11179. PMID 16807228. UNESCO Media Services (17 May ... From insulin to lysosomes". Hormones (Athens, Greece). 5 (2): 151-55. doi:10.14310/horm.2002.11179. PMID 16807228. Raju, TN ( ...
Lysosomes, Plasma membrane ----> Endosomes (receptor-mediated endocytosis) Membrane transport protein Wikipedia:MeSH D12.776# ...
LysosomesEdit. *Lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a ... Lysosomes are also used to destroy defective or damaged organelles in a process called autophagy. They fuse with the membrane ... These food vacuoles fuse with lysosomes which break down the components so that they can be used in the cell. This form of ... Most of these proteins mature in the Golgi apparatus before going to their final destination which may be to lysosomes, ...
Sharma J, di Ronza A, Lotfi P, Sardiello M (July 2018). "Lysosomes and Brain Health". Annual Review of Neuroscience. 41: 255- ... a protein that acts as a master regulator of the autophagy-lysosome pathway. Biostasis Cryoprotectant Cryptobiosis Freeze ...
Roy AB (April 1976). "Sulphatases, lysosomes and disease". The Australian Journal of Experimental Biology and Medical Science. ...
Roy AB (1976). "Sulphatases, lysosomes and disease". Aust. J. Exp. Biol. Med. Sci. 54 (2): 111-35. doi:10.1038/icb.1976.13. ...
It stains lysosomes red. It is used as a general stain in histology, as a counterstain in combination with other dyes, and for ... In the Neutral Red Assay live cells incorporate neutral red into their lysosomes. As cells begin to die, their ability to ... Vital staining of lysosomes and other cell organelles of the rat with Neutral red]. Progress in Histochemistry and ...
The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome. BioGPS analysis for ... with the N-terminus of the protein being within the lysosome and the C-terminus located in the cytosol. Post-translational ... "The Proteome of Lysosomes". Proteomics. 10 (22): 4053-4076. doi:10.1002/pmic.201000196. PMID 20957757. S2CID 25869334. Schroder ...
... lysosome; mitochondrion (inner and outer membranes); nucleus (inner and outer membranes); peroxisome; vacuole; cytoplasmic ...
For instance, lysosomes contain digestive enzymes that break down most biomolecules in the cytoplasm. Peroxisomes are used to ... "Lysosome". British Society for Cell Biology. Archived from the original on 13 November 2017. Retrieved 12 November 2017. ... and single membrane structures such as lysosomes. Mitochondria are proposed to come from the endosymbiosis of an aerobic ...
1976) Lysosomes in Biology and Pathology, Vol. 5. Elsevier, Amsterdam (pp. 404). Dingle, J.T., Dean, R.T., and Sly, W. eds. ( ... 1975) Lysosomes in Biology and Pathology, Vol. 4. Elsevier, Amsterdam (pp. 614). Dingle, J.T. and Dean, R.T. eds. ( ... 1984) Lysosomes in Biology and Pathology, Vol. 7. Elsevier, Amsterdam (pp. 479). Smith, H. and Dean, R.T. (1997) Improvisation ... 443). Dean, R.T. (1977) Lysosomes. Institute of Biology Series, Edward Arnold, London (pp. 90). Dean, R.T. (1978) Cellular ...
Cathelicidins, antimicrobial polypeptides found in lysosomes. Svendsen A (2000). "Lipase protein engineering". Biochim Biophys ...
... degradation occurs in the lysosomes. Here, arylsulfatase A hydrolyzes the sulfate group. However, in order for this ...
II . Bidirectional flow between secondary lysosomes and plasma membrane. J. Cell Biol. 86:304-314. With C. F. Nathan and H. W. ... V. The formation of macrophage lysosomes. J. Exp. Med. 123:757-766. 1967 With B. A. Ehrenreich. The uptake and digestion of ... These discoveries, which traced the phagocytic digestive system to the fusion of phagocytic vacuoles and lysosomes, became ... and fuses with the lysosome where the contents are then digested." The result, as Moberg and Steinman put it, was the ...
Janoff A, Scherer J (November 1968). "Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules ...
... s have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain ... Endosomes and lysosomes then fuse with the phagosome to contribute to the membrane, especially when the engulfed particle is ... Roy CR, Kagan JC (1 January 2013). Evasion of Phagosome Lysosome Fusion and Establishment of a Replicative Organelle by the ... They control actin polymerisation which is required for the phagosome to fuse with endosomes and lysosomes. Other non- ...
Upon activation by Rheb, mTORC1 localizes to the Ragulator-Rag complex on the lysosome surface where it then becomes active in ... Efeyan A, Zoncu R, Sabatini DM (September 2012). "Amino acids and mTORC1: from lysosomes to disease". Trends in Molecular ... Active mTORC1 is positioned on lysosomes. mTOR is inhibited when lysosomal membrane is damaged by various exogenous or ... At this stage another galectin, galectin-3, interacts with TRIM16 to guide selective autophagy of damaged lysosomes. TRIM16 ...
They are subsequently degraded in lysosomes. The remaining free amino acids are transported across the basolateral membrane by ...
When a macrophage ingests a pathogen, the pathogen becomes trapped in a phagosome, which then fuses with a lysosome. Within the ... Under normal circumstances, this phagocytic vacuole would develop into a lysosome and its contents would be digested. ... can remain latent in a macrophage via inhibition of phagosome-lysosome fusion; causes brucellosis (undulant fever). Legionella ... Mishima Y (October 1967). "Lysosomes in malanin phagocytosis and synthesis". Nature. 216 (5110): 67. Bibcode:1967Natur.216... ...
Organelles and bits of cytoplasm are sequestered and targeted for degradation by the lysosome for hydrolytic digestion by a ... Ashford and Porter used electron microscopy to observe mitochondrial fragments in liver lysosomes by 1962, and a 1977 report ... This turnover process consists of the sequestration and hydrolytic degradation by the lysosome, a process also known as ... Ashford, TP; Porter, KR (1962). "Cytoplasmic components of hepatic cell lysosomes". The Journal of Cell Biology. 12: 198-202. ...
Mutations of synuclien alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... "The Discovery of Lysosomes and Autophagy". 49. 3: 49. 2010. *^ Bandyopadhyay U, Kaushik S, Varticovski L, Cuervo AM (September ... De Duve, C (1983). "Lysosomes revisited". European Journal of Biochemistry / FEBS. 137 (3): 391-7. doi:10.1111/j.1432-1033.1983 ... With his student Peter, he established that lysosomes are responsible for glucagon-induced autophagy.[16][17] This was the ...
... this functionality can be used for optogenetic acidification of lysosomes and synaptic vesicles when targeted to these ... "Optogenetic acidification of synaptic vesicles and lysosomes". Nature Neuroscience. 18 (12): 1845-1852. doi:10.1038/nn.4161. ...
The lancet sperm sometimes contain many lysosomes. Some Sculpin may be sperm heteromorphic. Their ejaculates appear to contain ...
Lysosome: The lysosome functions to degrade material brought in from the outside of the cell or old organelles. This contains ... Autophagy is the process of degradation through lysosomes which occurs when a vesicle buds off from the ER and engulfs the ... Verity, M A. Lysosomes: some pathologic implications. OCLC 679070471. Cooper, Geoffrey M. (2000). "Transport of Small Molecules ... material, then, attaches and fuses with the lysosome to allow the material to be degraded. Ribosomes: Functions to translate ...
Researchers believe that this protein plays a role in the transport (trafficking) of materials into lysosomes. Lysosomes act as ... Although the lysosomal trafficking regulator protein is involved in the normal function of lysosomes, its exact role is unknown ... As a result of disordered intracellular trafficking there is impaired lysosome degranulation with phagosomes, so phagocytosed ... The disease is characterised by large lysosome vesicles in phagocytes (neutrophils), which thus have poor bactericidal function ...
... RNAi also disperse endosomes and lysosomes. Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for ...
The size of lysosomes varies from 0.1 μm to 1.2 μm. With a pH ranging from ~4.5-5.0, the interior of the lysosomes is acidic ... Vacuoles do not have catabolic activity and do not undergo exocytosis as lysosomes do. The word lysosome (/ˈlaɪsoʊsoʊm/, / ... doi:10.1146/knowable-121118-1. Lüllmznn-Rauch R (2005). "History and Morphology of Lysosome". In Zaftig P (ed.). Lysosomes ( ... "The crucial impact of lysosomes in aging and longevity". Ageing Research Reviews. Lysosomes in Aging. 32: 2-12. doi:10.1016/j. ...
GFP-like proteins stably accumulate in lysosomes.. Katayama H1, Yamamoto A, Mizushima N, Yoshimori T, Miyawaki A. ... In this study, we demonstrate that these structures are not cytosolic aggregates but lysosomes that have accumulated the GFP- ... and immunocytochemical experiments have revealed that certain GFP-like proteins expressed in the cytosol enter lysosomes ...
... we will explore the contributions lysosomes play in inducing cell death, how this is regulated by ROS in cancer, and how ... Lysosomes are membrane-bound vesicles that contain hydrolases for the degradation and recycling of essential nutrients to ... 5. Lysosome-Mediated Cell Death (LCD). Since their discovery as the suicide bags of the cell, lysosomes have been explored as ... The damaged lysosomes are engulfed by autophagosomes which then fuse with functional lysosomes to remove them from the cells [ ...
Lysosome definition, a cell organelle containing enzymes that digest particles and that disintegrate the cell after its death. ... lysosome. in Science. lysosome. [lī′sə-sōm′]. *A cell organelle that is surrounded by a membrane, has an acidic interior, and ... Origin of lysosome. First recorded in 1950-55; lyso- + -some3. Related formsly·so·so·mal, adjective. Dictionary.com Unabridged ... lysosome. in Medicine. lysosome. [lī′sə-sōm′]. n.. *A membrane-bound organelle in the cytoplasm of most cells containing ...
The lumen of a lysosome is the volume enclosed within the lysosomal membrane. ...
Lysosomes - By: Scott Jakobsze by Scott Jakobsze , This newsletter was created with Smore, an online tool for creating ...
Triazoles inhibit cholesterol export from lysosomes by binding to NPC1. Michael N. Trinh, Feiran Lu, Xiaochun Li, Akash Das, ... Triazoles inhibit cholesterol export from lysosomes by binding to NPC1 Message Subject (Your Name) has sent you a message from ... 2A shows that posaconazole and P-X are potent inhibitors of cholesterol export from lysosomes, as reflected in the cholesterol ... The ability of various compounds to block the NPC1-mediated export of cholesterol from lysosomes was tested using a cholesterol ...
Here we demonstrate that the cellular degradative machinery-including lysosomes, autophagosomes, mitophagosomes and the protein ... 3: Lysosomes, autophagosomes and mitophagosomes are co-inherited during asymmetric HSC divisions and predict upregulation of ... 6 NUMB and lysosomes colocalize partially and are co-inherited.. a, Freshly isolated KSL cells were sorted, cultured in 100 ng ... Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells. *Dirk Loeffler1,2. , ...
Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact ... Structurally, the lamp proteins consist of two internally homologous lysosome-luminal domains separated by a proline-rich hinge ...
The size of lysosomes varies from 0.1 μm to 1.2 μm.[16] With a pH ranging from 4.5 to 5.0, the interior of the lysosomes is ... The word lysosome (/ˈlaɪsoʊsoʊm/, /ˈlaɪzəzoʊm/) is New Latin that uses the combining forms lyso- (referring to lysis and ... Lysosomes are known to contain more than 60 different enzymes.[4][5] Enzymes of the lysosomes are synthesised in the rough ... A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. The lumens pH (4.5-5.0)[1] is ...
While lysosome-like, this structure is not a typical lysosome that is devoid of MPRs. The endocytic marker alpha 2 ... The mannose 6-phosphate receptor and the biogenesis of lysosomes.. Griffiths G1, Hoflack B, Simons K, Mellman I, Kornfeld S. ... most of the marker was transported from the structure into lysosomes. We propose that the MPR/lgp-enriched structure is a ... lysosomal enzymes are released from the MPR and packaged along with newly synthesized lysosomal glycoproteins into lysosomes. ...
Lysosomes are small vesicles that contain a variety of acidic hydrolase enzymes capable of disposing of biological material ... The enzymes contained within a lysosome are strong enough to kill the host cell if not contained within the lysosomes membrane ... A cell may contain hundreds of lysosomes. Lysosomes are only found within certain complex cells known as eukaryotes, which ... Lysosomes are located within a cells cytoplasm, which is a liquid layer contained by the outer cell membrane. Many of a cells ...
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... lysosomes showed that the lysosomes from glands undergoing involution had increased permeability compared with lysosomes from ...
Plasmid mTurquoise-Lysosomes-20 from Dr. Michael Davidsons lab contains the insert LAMP1. This plasmid is available through ... mTurquoise-Lysosomes-20 was a gift from Michael Davidson (Addgene plasmid # 55568 ; http://n2t.net/addgene:55568 ; RRID:Addgene ...
tags: lysosomes x microbiology x culture x disease/medicine x The Scientist. » lysosomes, microbiology, culture and disease/ ...
tags: lysosomes x evolution x ecology x genetics & genomics x The Scientist. » lysosomes, evolution, ecology and genetics & ...
Lysosome 3D models for download, files in 3ds, max, c4d, maya, blend, obj, fbx with low poly, animated, rigged, game, and VR ...
The results confirm and extend the conclusion, derived from previous investigations on normal animals, that the lysosomes of ...
... Nature. 2010 Jun 17;465(7300):942-6. doi: 10.1038/ ... In autophagy, double-membrane autophagosomes envelop and sequester intracellular components and then fuse with lysosomes to ... Thus, an evolutionarily conserved cycle in autophagy governs nutrient sensing and lysosome homeostasis during starvation. ... thereby restoring the full complement of lysosomes in the cell-a process we identify in multiple animal species. ...
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Lysosome. Yale University. [2] *↑ 3.0 3.1 Fullick, Ann (2008). Edexcel AS Biology Students Book. pp. 142-143. ISBN 978-1-4058- ... A lysosome is a cell organelle.[1] They are like spheres. They have hydrolytic enzymes which can break down almost all kinds of ... By convention, lysosome is the term used for animal cells.[2] In plant cells, vacuoles do similar functions. With a wider ... Lysosomes work like the digestive system to break down, or digest, proteins, acids, carbohydrates, dead organelles, and other ...
Lysosome - Schistosoma mansoni [ Pathway menu , Organism menu , Pathway entry , Download KGML , Show description , User data ... Lysosomes are membrane-delimited organelles in animal cells serving as the cells main digestive compartment to which all sorts ... Substances for digestion are acquired by the lysosomes via a series of processes including endocytosis, phagocytosis, and ...
The size of lysosomes varies from 0.1-1.2 μm. At pH 4.8, the interior of the lysosomes is acidic compared to the slightly ... Lysosome. Lysosomes are cellular organelles that contain acid hydrolase enzymes to break down waste materials and cellular ... Lysosomes digest excess or worn-out organelles, food particles, and engulf viruses or bacteria. The membrane around a lysosome ... The name lysosome derives from the Greek words lysis, to separate, and soma, body. They are frequently nicknamed "suicide-bags ...
Study Shows Lysosomes Greatly Accelerate Formation of Amyloid Plaques New research from Yale University shows that increased ... lysosomes in neural projections in a mouse model of Alzheimers greatly accelerated formation of amyloid plaques. Lysosomes… ...
Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion. Irmina A. Elliott, Amanda M. ... Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion. Irmina A. Elliott, Amanda M. ... Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion Message Subject (Your Name) has ... Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion. Irmina A. Elliott, Amanda M. ...
However, BNIP3 did not target to lysosomes by subcellular fractionation, provoke lysosome permeabilization or alter lysosome pH ... Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death Autophagy. 2012 Mar;8(3):297-309. doi: 10.4161/auto. ... Rather, BNIP3-induced autophagy caused a decline in lysosome numbers with decreased expression of the lysosomal protein LAMP-1 ... Forced expression of transcription factor EB (TFEB) in BNIP3-expressing cells increased lysosome numbers, decreased ...
Endosomes and Lysosomes: A Dynamic Relationship, 1993, Buch, 978-1-55938-362-2. Bücher schnell und portofrei ... Our understanding of endosomes and lysosomes has undergone a molecular revolution over the last decade. Hence, we now know much ... The dynamic nature of the relationship between endosomes and lysosomes is the unifying focus of the genetic, biochemical, ... In this volume current molecular knowledge concerning the function and relationship of endosomes and lysosomes is presented. ...
... on WN Network delivers the latest Videos and Editable pages for News & Events, including Entertainment, Music, Sports ... Lysosome. A lysosome (derived from the Greek words lysis, meaning "to loosen", and soma, "body") is a membrane-bound cell ... Latest News for: lysosome. Edit Receptor-like role for PQLC2 amino acid transporter in the lysosomal sensing of cationic amino ... Furthermore, lysosomes are responsible for cellular homeostasis for their involvements in secretion, plasma membrane repair, ...
7 in The Journal of Cell Biology, suggests that developing ways to restore lysosome transport could represent a new therapeutic ... Researchers from Yale University School of Medicine have discovered that defects in the transport of lysosomes within neurons ... In neurons, lysosomes are thought to "mature" as they are transported from the ends of axons to the neuronal cell body, ... The lysosomes that get stuck and accumulate inside the axonal swellings associated with amyloid plaques fail to properly mature ...
  • The mannose 6-phosphate receptor and the biogenesis of lysosomes. (nih.gov)
  • Lysosome biogenesis is linked to the to the secretory and endocytic pathways for protein and lipid trafficking. (ebi.ac.uk)
  • One of the protein complexes involved in this process is biogenesis of lysosome-related organelles complex 1 (BLOC-1). (ebi.ac.uk)
  • Lysosomes 'host' multiple stress-sensing mechanisms that trigger the coordinated biogenesis of autophagosomes and lysosomes. (sigmaaldrich.com)
  • For example, transcription factor (TF)EB, which regulates autophagy and lysosome biogenesis, is activated following the inhibition of mTOR, a lysosome-localized nutrient sensor. (sigmaaldrich.com)
  • This activation triggers calcineurin-dependent TFEB-nuclear translocation, autophagy induction and lysosome biogenesis. (sigmaaldrich.com)
  • TFEB, for example, is a known regulator of lysosome biogenesis. (novusbio.com)
  • However, specialized secretory vesicles regulated by Ca2+, such as neutrophil azurophil granules, mast cell-specific granules, and cytotoxic lymphocyte lytic granules, share characteristics with lysosomes that may reflect a common biogenesis. (nih.gov)
  • Here we demonstrate that the cellular degradative machinery-including lysosomes, autophagosomes, mitophagosomes and the protein NUMB-can be asymmetrically inherited into haematopoietic-stem-cell daughter cells. (nature.com)
  • Fig. 3: Lysosomes, autophagosomes and mitophagosomes are co-inherited during asymmetric HSC divisions and predict upregulation of CD71. (nature.com)
  • In autophagy, double-membrane autophagosomes envelop and sequester intracellular components and then fuse with lysosomes to form autolysosomes, which degrade their contents to regenerate nutrients. (nih.gov)
  • Forced expression of transcription factor EB (TFEB) in BNIP3-expressing cells increased lysosome numbers, decreased autophagosomes and increased autolysosomes, prevented p62 accumulation, removed depolarized mitochondria and attenuated BNIP3-induced death. (nih.gov)
  • Loss of spastizin or spatacsin resulted in depletion of free lysosomes, which are competent to fuse with autophagosomes, and an accumulation of autolysosomes, reflecting a failure in ALR. (jci.org)
  • In this manner TFEB can regulate energy metabolism by influencing the levels of lysosomes and autophagosomes within the cell in response to nutrient levels (1). (novusbio.com)
  • The lack of lysosomes in the axon also affected cell structures called autophagosomes, which deliver their contents to lysosomes for disposal. (nih.gov)
  • Without lysosomes, autophagosomes accumulated and remained stationary, unable to discard their contents. (nih.gov)
  • Protein found in the lysosome, a membrane-limited organelle present in all eukaryotic cells, which contains a large number of hydrolytic enzymes that are used for the intracellular degradation of macromolecules. (uniprot.org)
  • Lysosomes are membrane-bound vesicles that contain hydrolases for the degradation and recycling of essential nutrients to maintain homeostasis within cells. (hindawi.com)
  • Lysosomes are membrane-delimited organelles in animal cells serving as the cell's main digestive compartment to which all sorts of macromolecules are delivered for degradation. (genome.jp)
  • Lysosomes are membrane-bound organelles found in animals that are involved in degradation of endogenous and exogenous macromolecules [ PMID: 15261680 ]. (ebi.ac.uk)
  • Lysosomal membrane markers serve as tools for tracking fusion with the autophagosome prior to degradation of the autolysosome contents, whereas cell permeable LysoTracker® dyes target acidic organelles and are localized within the lysosomes in nanomolar concentrations. (thermofisher.com)
  • Lysosomes are small specialized organelles containing a variety of different hydrolase enzymes that are responsible for degradation of all macromolecules, entering the cells through the endosomal system or originated from the internal sources. (wingsforlife.com)
  • Thus, it is likely that the down-regulation and degradation of Fc receptors which occurs during the endocytosis of antibody-antigen complexes is due to the transport of internalized receptors to lysosomes. (rupress.org)
  • Based on our findings, we conclude that endogenous, wild-type presenilins are necessary for proper protein degradation through the autophagosome-lysosome system by functioning at the lysosomal level. (jneurosci.org)
  • Macroautophagy, hereafter referred to as autophagy, involves the sequestration of cellular contents by an autophagosome and subsequent fusion of the autophagosome to a lysosome for degradation of its contents. (jneurosci.org)
  • Within a cell, lysosomes must move around to survey the cell's contents and identify targets for degradation or other actions. (nih.gov)
  • We show that these proteins function in different steps of lysosome biology, regulating lysosome formation, lysosome fusion, and lysosome degradation. (g3journal.org)
  • Release mechanisms such as proteolytic degradation of the antibody in the lysosomes or cleavage of the linker connecting the antibody and the drug by specific intracellular processes have been proposed. (aacrjournals.org)
  • To examine the role of lysosomes in the degradation of skeletal-muscle myofibrillar proteins, we measured the release of N tau-methylhistidine from perfused muscle of starved and fed rats in the presence or absence of agents that inhibit lysosomal proteinase activity. (biochemj.org)
  • Supplementary Materials p.5 right column bottom paragraph:'Degradation in a lysosome may cost essentially nothing, but amino-acid export back to the cytoplasm consumes ~1 ATP for every 3 to 4 amino acids. (harvard.edu)
  • After substances, such as cellular wastes, old organelles, fats, carbohydrates and proteins, are broken down in the lysosomes, the products are then released back into the cytoplasm to become the raw materials for the making of new substances and cellular structures. (reference.com)
  • Lysosomes are often termed the garbage disposal of the cell, but as our knowledge and understanding increase, the roles lysosomes play in other cellular functions expand [ 2 ]. (hindawi.com)
  • The enzymes found in lysosomes are produced by cellular components known as ribosomes, which are then safely packaged within their vesicular membrane in a region of a cell known as the Golgi apparatus. (reference.com)
  • Lysosomes are cellular organelles that contain acid hydrolase enzymes to break down waste materials and cellular debris. (medicalxpress.com)
  • Furthermore, lysosomes are responsible for cellular homeostasis for their involvements in secretion, plasma membrane repair, cell signalling and energy metabolism , which are related to health and diseases. (wn.com)
  • These axonal swellings are packed with lysosomes, cellular garbage disposal units that degrade old or damaged components of the cell. (eurekalert.org)
  • You can observe lysosomes-RFP behavior in live cells independently of organelle pH and label with multiple tracking or tracing dyes to image dynamic cellular processes. (thermofisher.com)
  • CellLight® Lysosomes-RFP, BacMam 2.0, is a fusion construct of Lamp1 (lysosomal associated membrane protein 1) and TagRFP, providing accurate and specific targeting to cellular lysosomes-RFP. (thermofisher.com)
  • The function of breaking down cellular contents is done by the lysosome. (varsitytutors.com)
  • Lysosomes are cellular sanitation engineers that help clean up and recycle internal debris no longer needed by cells. (scitechdaily.com)
  • Imipramine was further found to specifically increase the cellular accumulation of amine-containing substrates of lysosomal ion trapping (LysoTracker Green, daunorubicin, methylamine, propranolol) but not compounds that don't accumulate by ion trapping in lysosomes, suggesting that the drug-induced lipidosis specifically increases the cellular accumulation of drugs that accumulate in lysosomes. (ku.edu)
  • Although lysosomes perform a number of essential cellular functions, damaged lysosomes represent a potential hazard to the cell. (uio.no)
  • These findings highlight a novel role for lysosomes in cellular membrane traffic and suggest that fusion of lysosomes with the plasma membrane may be an ubiquitous form of Ca2+-regulated exocytosis. (nih.gov)
  • The findings show that uneven distribution of lysosomes disrupts essential cellular processes in neurons. (nih.gov)
  • A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. (wikipedia.org)
  • Lysosomes are known to contain more than 60 different enzymes, and have more than 50 membrane proteins. (wikipedia.org)
  • Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum and exported to the Golgi apparatus upon recruitment by a complex composed of CLN6 and CLN8 proteins. (wikipedia.org)
  • GFP-like proteins stably accumulate in lysosomes. (nih.gov)
  • In this study, we demonstrate that these structures are not cytosolic aggregates but lysosomes that have accumulated the GFP-like proteins. (nih.gov)
  • Our biochemical and immunocytochemical experiments have revealed that certain GFP-like proteins expressed in the cytosol enter lysosomes possibly by an autophagy-related mechanism, but retain their fluorescence because of resistance not only to acidity but also to lysosomal proteases. (nih.gov)
  • The most abundant lysosomal membrane proteins are lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2). (hindawi.com)
  • Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. (wikipedia.org)
  • The identification of other proteins that function alongside JIP3 in regulating the axonal transport and maturation of lysosomes could ultimately lead to strategies to modulate the axonal abundance of lysosomes for therapeutic purposes," Ferguson says. (eurekalert.org)
  • They are used for the digestion of macromolecules from phagocytosis (ingestion of other dying cells or larger extracellular material, like foreign invading microbes), endocytosis (where receptor proteins are recycled from the cell surface), and autophagy (wherein old or unneeded organelles or proteins, or microbes that have invaded the cytoplasm are delivered to the lysosome). (thefullwiki.org)
  • There are a number of lysosomal storage diseases that are caused by the malfunction of the lysosomes or one of their digestive proteins, e.g. (thefullwiki.org)
  • In the cells, disposing of "garbage" or cell waste such as damaged proteins is accomplished by the lysosome, organelles that are present in nearly every cell. (emaxhealth.com)
  • The organelle most closely associated with the manufacture of proteins within the cell is the A. ribosome B. lysosome C. nucl. (coursehero.com)
  • Both membrane proteins and Lysotracker dyes serve as effective tools for tracking lysosome behavior. (thermofisher.com)
  • We also review lysosome biosynthesis, showing how recent studies of lysosome-like organelles including the yeast vacuole, Drosophila eye pigment granules and mammalian secretory lysosomes have identified novel proteins involved in this process. (biologists.org)
  • Targeting proteins to secretory lysosomes of natural killer cells as a principle for immunoregulation. (lu.se)
  • We asked whether one could target exogenous proteins to the secretory lysosomes of NK-cells for final delivery into a tumor site upon degranulation. (lu.se)
  • Expression of exogenous normally secretory non-membrane proteins, such as alpha1-microglobulin (alpha1-m) and alpha1-antitrypsin (alpha1-at) resulted mostly in constitutive secretion although a small amount of alpha1-microglobulin was targeted to secretory lysosomes. (lu.se)
  • Blocking phosphorylation reduces trafficking to the lysosome, stabilizing PI4KIIalpha and its cargo proteins for redistribution throughout the cell. (garvan.org.au)
  • Some proteins help lysosomes move along microtubules to a cell's periphery, while other proteins help them move toward the center. (nih.gov)
  • Importantly, they also identified a group of proteins-the BORC complex (made up of 8 smaller proteins), Arl8b, SKIP, and kinesin-1-that are responsible for the transportation of lysosomes into the axon area of neurons. (nih.gov)
  • When the researchers eliminated or disrupted these proteins, the concentration of lysosomes in the axon decreased. (nih.gov)
  • SiR700-lysosome is compatible in dual fluorescence studies with other SIR dye conjugates, GFP and/or mCherry fluorescent proteins. (cytoskeleton.com)
  • ATPase levels were decreased, we observed lysosome association of MTOR and normal signaling of MTORC1 despite an increase in autophagic marker proteins. (figshare.com)
  • Lysosomes usually originate from the pinching off of the Golgi apparatus, but they can also arise from endosomes. (reference.com)
  • The enzymes are trafficked from the Golgi apparatus to lysosomes in small vesicles, which fuse with larger acidic vesicles. (wikipedia.org)
  • in the center of the top image, a Golgi Apparatus can be seen, distal from the cell membrane relative to the lysosomes. (wikipedia.org)
  • It lacks peroxisomes, a classical Golgi apparatus, and canonical lysosomes. (pubmedcentralcanada.ca)
  • Increased mTOR activity attenuates autophagy and generates proto-lysosomal tubules and vesicles that extrude from autolysosomes and ultimately mature into functional lysosomes, thereby restoring the full complement of lysosomes in the cell-a process we identify in multiple animal species. (nih.gov)
  • Thus, an evolutionarily conserved cycle in autophagy governs nutrient sensing and lysosome homeostasis during starvation. (nih.gov)
  • Substances for digestion are acquired by the lysosomes via a series of processes including endocytosis, phagocytosis, and autophagy. (genome.jp)
  • Rather, BNIP3-induced autophagy caused a decline in lysosome numbers with decreased expression of the lysosomal protein LAMP-1, indicating lysosome consumption and consequent autophagosome accumulation. (nih.gov)
  • cytoplasmic lipid droplets (LDs) in the lysosome-directed process of autophagy. (wn.com)
  • MCOLN1 is a ROS sensor in lysosomes that regulates autophagy. (sigmaaldrich.com)
  • Recent studies have shown that autophagy plays a When chloroquine enters the lysosome, it becomes protonated because of the low pH within the lysosome, and. (musicaenlamochila.net)
  • However, autophagosome-lysosome fusion was impaired due to altered levels of LAMP-1, AMPK and ULK-1, resulting in autophagosome accumulation (incomplete autophagy). (uio.no)
  • Niemann-Pick C1 (NPC1), a membrane protein of lysosomes, is required for the export of cholesterol derived from receptor-mediated endocytosis of LDL. (pnas.org)
  • This protein complex controls multiple aspects of lysosome function . (wn.com)
  • Researchers from Yale University School of Medicine have discovered that defects in the transport of lysosomes within neurons promote the buildup of protein aggregates in the brains of mice with Alzheimer's disease. (eurekalert.org)
  • One possibility is that they promote the buildup of β-amyloid because some of the enzymes that generate β-amyloid by cleaving a protein called amyloid precursor protein (APP) accumulate in the swellings with the immature lysosomes. (eurekalert.org)
  • The researchers found that neurons lacking a protein called JIP3 failed to transport lysosomes from axons to the cell body, leading to the accumulation of lysosomes in axonal swellings similar to those seen in Alzheimer's disease patients. (eurekalert.org)
  • Here, we have demonstrated that the two most common autosomal recessive hereditary spastic paraplegia gene products, the SPG15 protein spastizin and the SPG11 protein spatacsin, are pivotal for autophagic lysosome reformation (ALR), a pathway that generates new lysosomes. (jci.org)
  • Clioquinol, an anti-parasitic medication, overcomes the effect of mutations in the LRRK2 gene associated with Parkinson's disease by restoring the acidity of lysosomes and clearing out protein aggregates. (neurosciencenews.com)
  • CellLight® Lysosomes-RFP, BacMam 2.0, provides an easy way to label lysosomes with red fluorescent protein (RFP) in live cells. (thermofisher.com)
  • Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. (scitechdaily.com)
  • These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects. (scitechdaily.com)
  • Amyloid-β oligomers, which are precursors of amyloid plaques in AD brain and stimulate mTORC1 protein kinase activity at the plasma membrane, but not at lysosomes, block this nutrient-induced mitochondrial activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in AD brain. (ssrn.com)
  • Erythromycin, a potent inhibitor of bacterial protein synthesis, at a concentration that completely inhibits L. pneumophila intracellular multiplication, had no influence on fusion of L. pneumophila phagosomes with secondary lysosomes. (rupress.org)
  • GSK3 phosphorylates two distinct sites in the N-terminus of PI4KIIalpha (Ser5 and Ser47), promoting binding to the adaptor protein 3 (AP-3) complex for trafficking to the lysosome to be degraded. (garvan.org.au)
  • For example, genetic screens in yeast have identified a group of genes encoding the Class C vacuolar protein sorting (VPS) 5 complex, which is involved in the docking and membrane fusion of endosomal vesicles and the lysosome-like yeast vacuole. (pubmedcentralcanada.ca)
  • They also suggest that total proteolysis, which primarily reflects non-myofibrillar protein breakdown, occurs at least in part within lysosomes. (biochemj.org)
  • Two motifs target batten disease protein CLN3 to lysosomes in transfected nonneuronal and neuronal cells. (julkari.fi)
  • A striking microscopic feature of stingray alkaline gland epithelial cells was large secondary lysosomes that imparted a dark green-black color to the gland and were distinctive in unstained tissue sections. (thefreedictionary.com)
  • The presence of thyroglobulin indicates that the lysosome population is probably composed of primary and secondary lysosomes. (portlandpress.com)
  • Phagosomes containing live L. pneumophila did not fuse with secondary lysosomes at 1 h after entry into monocytes or at 4 or 8 h after entry by which time the ribosome-lined L. pneumophila replicative vacuole had formed. (rupress.org)
  • In contrast, the majority of phagosomes containing formalin-killed L. pneumophila, live Streptococcus pneumoniae, and live Escherichia coli had fused with secondary lysosomes by 1 h after entry into monocytes. (rupress.org)
  • Also activating the monocytes promoted fusion of a small proportion of phagosomes containing live L. pneumophila with secondary lysosomes. (rupress.org)
  • Acid phosphatase cytochemistry revealed that phagosomes containing live L. pneumophila did not fuse with either primary or secondary lysosomes. (rupress.org)
  • We conclude that BNIP3 expression induced autophagosome accumulation with lysosome consumption in cardiomyocytes. (nih.gov)
  • We tested the hypothesis that the efficiency of LY transfer between the pinosomal and lysosomal compartments is increased in the presence of tubular lysosomes by asking how conditions that deplete the tubular lysosome network affect pinocytic accumulation of LY. (rupress.org)
  • We conclude that a basal level of solute accumulation via pinocytosis proceeds independently of the tubular lysosomes, and that an extended tubular lysosomal network contributes to the elevated rates of solute accumulation that accompany macrophage stimulation. (rupress.org)
  • Aberrant lysosomal targeting causes inclusion-cell disease , whereby enzymes do not properly reach the lysosome, resulting in accumulation of waste within these organelles. (thefullwiki.org)
  • To study the effects of lysosomal dysfunction in ARPE-19, it was necessary to establish an in vitro model utilizing chloroquine lysosome accumulation theory postu- lates that the monoprotonated form of chloroquine enters the lysosome, where it becomes diprotonated and trapped. (musicaenlamochila.net)
  • Determination of lysosome specific accumulation of LTR in cells with or without an intact lysosomal pH gradient revealed that imipramine caused an approximately three-fold increase in the lysosome-specfic uptake of LTR. (ku.edu)
  • However, these results are consistent with an increased aqueous volume of lysosomes resulting in increased drug accumulation. (ku.edu)
  • These results suggest that the accumulation of lipophilic basic drugs is driven primarily by the transmembrane pH difference (pH-partition theory) but with the involvement of some additional mechanism(s) related to drug lipophilicity, possibly binding (partition or adsorption) to lipophilic substance(s) and/or aggregation within lysosomes. (aspetjournals.org)
  • This encapsulation improved the water solubility, overcame the quenching effects in water, as well as allowed selective accumulation in the lysosomes with a bright fluorescence signal in monolayer cells as well as 3D multicellular tumor spheroids (MCTS). (uzh.ch)
  • Accumulation of acridine orange in the lysosomes of each cell line was determined using flow cytometry completed at 4 and 6 hours-post irradiation. (banglajol.info)
  • Abstract: Lysosomes robustly accumulate within axonal swellings at Alzheimer's disease (AD) amyloid plaques. (scitechdaily.com)
  • Lysosomes have an acidic interior, which is useful for breaking down macromolecules that are no longer being used in the cell. (varsitytutors.com)
  • Proton pumps use ATP to continuously pump hydrogen ions into the interior of the lysosome, thus maintaining an acidic environment in which the enzymes are most optimally efficient at breaking down the debris/macromolecules. (varsitytutors.com)
  • This has a led to a hypothesis that dense core lysosomes are in essence storage granules for acid hydrolases and that, when the former fuse with late endosomes, a hybrid organelle for digestion of endocytosed macromolecules is created. (biologists.org)
  • The persistence of small foreign molecules in lysosomes described by Dr Dingle stands quite in contrast with the fast turnover of foreign macromolecules captured by these organelles. (royalsocietypublishing.org)
  • When a lysosome digests food, it meets up with a food vacuole and fuses with it, releasing its digesting enzymes into the vacuole. (reference.com)
  • In step two a lysosomes within an active hydrolytic enzyme comes into picture as the food vacuole moves away from the plasma membrane. (wikipedia.org)
  • Step three consists of the lysosome fusing with the food vacuole and hydrolytic enzymes entering the food vacuole. (wikipedia.org)
  • Dec 26, 2018 · What is a Lysosome The lysosome is a membrane-enclosed vacuole in the cytoplasm, containing hydrolytic enzymes. (musicaenlamochila.net)
  • Lysosomes act as the waste disposal system of the cell by digesting in used materials in the cytoplasm, from both inside and outside the cell. (wikipedia.org)
  • Lysosomes are located within a cell's cytoplasm, which is a liquid layer contained by the outer cell membrane. (reference.com)
  • Many of a cell's essential components are located within the cytoplasm, protected internally by lysosomes and externally by the cell membrane. (reference.com)
  • When the organic components of a cell become obsolete, lysosomes carry out the task of removing them from the cytoplasm. (reference.com)
  • With a wider definition, lysosomes are found in the cytoplasm of plant and protists as well as animal cell . (wikipedia.org)
  • Thus lysosomes act as the waste disposal system of the cell by digesting unwanted materials in the cytoplasm , both from outside of the cell and obsolete components inside the cell. (wn.com)
  • A network of tubular lysosomes extends through the cytoplasm of J774.2 macrophages and phorbol ester-treated mouse peritoneal macrophages. (rupress.org)
  • Lysosomes keep cells clean and recycle materials. (reference.com)
  • Although lysosomes dwell within all animal cells, many of them reside within white blood cells. (reference.com)
  • Because white blood cells encounter foreign invaders and pathogens, they must be able to render the invaders harmless by digesting them within their lysosomes. (reference.com)
  • A lysosome (/ˈlaɪsəˌsoʊm/) is a membrane-bound organelle found in many animal cells. (wikipedia.org)
  • Cells obtain cholesterol through receptor-mediated endocytosis of LDL into lysosomes. (pnas.org)
  • Fig. 4: Asymmetric lysosome inheritance predicts fate heterogeneity of HSC daughter cells. (nature.com)
  • A lysosome is a membrane-bound organelle found in many animal cells and most plant cells . (wikipedia.org)
  • Lysosomes are only found within certain complex cells known as eukaryotes, which contain nuclei and the other advanced organelles essential for cell function. (reference.com)
  • By convention, lysosome is the term used for animal cells. (wikipedia.org)
  • A lysosome (derived from the Greek words lysis , meaning "to loosen", and soma , "body") is a membrane-bound cell organelle found in most animal cells (they are absent in red blood cells ). (wn.com)
  • Cells that lack lysosome-related organelles express BLOC-1 but do not appear to need it for lysosome biosynthesis. (ebi.ac.uk)
  • Tubular lysosomes were disassembled in cells treated with microtubule-depolymerizing drugs or in cells that had phagocytosed latex beads. (rupress.org)
  • Lysosomes are the cells' garbage disposal system. (thefullwiki.org)
  • In the past, lysosomes were thought to kill cells that were no longer wanted, such as those in the tails of tadpoles or in the web from the fingers of a 3- to 6-month-old fetus . (thefullwiki.org)
  • His research focuses on the dysfunction of lysosomes which serve to rid the cells of waste products. (emaxhealth.com)
  • Against rheumatoid arthritis, it operates by inhibiting lymphocyte proliferation, phospholipase A2, antigen presentation in dendritic cells, release of enzymes from lysosomes, release of reactive oxygen species from macrophages, and production of chloroquine lysosome function IL-1. (musicaenlamochila.net)
  • Human osteosarcoma (U2OS) cells expressing CellLight® Lysosomes-GFP . (thermofisher.com)
  • Significantly, the resultant AIED with good membrane permeability has been successfully employed to visualize the endogenous H2S in lysosomes in living cells. (rsc.org)
  • Leishmania cells developed ways to sense the lysosome-specific environment (acidic pH and body temperature) as means of recognition and, subsequently, initiation of differentiation into the intracellular form. (frontiersin.org)
  • Isolated thyroid lysosomes should serve as an interesting model to study the reactions whereby thyroid hormones are generated from thyroglobulin and released into the thyroid cells. (portlandpress.com)
  • Effect of colchicine on the three-dimensional organization of elongated lysosomes(Nematolysosomes) in rat pancreatic exocrine cells. (nii.ac.jp)
  • Elucidation of the properties of endosomal and lysosomal membranes has clear biomedical significance, both from the point of view of hindering the progression of pathogens in cells and in understanding inherent pathological processes such as hereditary diseases concerning lysosomes. (jyu.fi)
  • The dysfunction of lysosomes, organelles that engulf and degrade nutrients and cell debris in most living cells, is associated with several human ailments, including Alzheimer's disease and Parkinson's disease, as well as certain rare genetic disorders. (uchicago.edu)
  • In "A DNA nanomachine chemically resolves lysosomes in live cells," published 3 December 2018 in Nature Nanotechnology , postdoc KaHo Leung, graduate students Kasturi Chakraborty and Anand Saminathan, and Professor Yamuna Krishnan use a DNA-based sensor to simultaneously measure levels of protons and chloride ions in lysosomes. (uchicago.edu)
  • Using this new technology the Krishnan lab identifies two different populations of lysosomes in cells of normal individuals, one of which is absent in cells derived from patients with Niemann-Pick disease. (uchicago.edu)
  • Treating diseased cells with the right therapeutic restores the lysosome distribution to that of healthy cells. (uchicago.edu)
  • With the help of the self-luminescence of complex Ir3 and confocal microscopy, it was observed that Ir3 efficiently penetrated into the A549 cells via energy-dependent active transport, and specifically accumulated in lysosomes, affected the permeabilization of the lysosomal membranes and induced caspase-dependent cell death through lysosomal damage. (rsc.org)
  • Recent data both from cell-free experiments and from cultured cells have shown that lysosomes can fuse directly with late endosomes to form a hybrid organelle. (biologists.org)
  • Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells. (nih.gov)
  • Exposure to the Ca2+ ionophore ionomycin or addition of Ca2+-containing buffers to streptolysin O-permeabilized cells induced exocytosis of approximately 10% of the total lysosomes of NRK cells.The process was also detected in other cell types such as epithelial cells and myoblasts.Lysosomal exocytosis was found to require micromolar levels of Ca2+ and to be temperature and ATP dependent, similar to Ca2+-regulated secretory mechanisms in specialized cells. (nih.gov)
  • Additionally, they observed that cells with low or absent presenilin-1 had decreased acidification of lysosomes attributable to dysfunctional glycosylation and targeting of the v-ATPase VOa1 subunit. (jneurosci.org)
  • Secretory lysosomes of natural killer (NK) cells combine storage, regulated secretion and lysosomal activity. (lu.se)
  • Damage to lysosomes possibly accounts for the selective toxicity of the compounds for monocytes, NK cells and cytotoxic T cells. (springer.com)
  • In complex cells like neurons , which consist of projections (called axons and dendrites) jutting out from the cell body, lysosome transport is not well understood. (nih.gov)
  • Lysosomes, the major membrane-bound degradative organelles, have a multitude of functions in eukaryotic cells. (g3journal.org)
  • Lysosomes are membrane-bound organelles that serve as the major degradative compartments for endocytic, phagocytic, and autophagic materials targeted for destruction in eukaryotic cells. (g3journal.org)
  • Live human fibroblast cells stained with 1 µM SiR700-lysosome (red) and Hoechst (blue) for 1 h at 37°C and imaged by widefield microscopy. (cytoskeleton.com)
  • It stains early and late endocytic vesicles and lysosomes in live cells without the need for genetic manipulation or overexpression. (cytoskeleton.com)
  • SiR700-lysosome can be used for widefield, confocal, SIM or STED imaging in living cells and tissue. (cytoskeleton.com)
  • Findings define a novel generalized strategy to target cancer cells by disrupting lysosome function in a selective manner that is associated with apoptosis induction and potent antitumor effects. (aacrjournals.org)
  • Thus, the aim of this present study is to determine the characteristics of lysosomes of cancerous and normal cells in response to low-energy/low-dose medical diagnostic X-rays. (banglajol.info)
  • The lysosome has a plasma membrane surrounding it, which protects the rest of the cell from the destructive enzymes contained within the organelle. (reference.com)
  • May function in protection of the lysosomal membrane from autodigestion, maintenance of the acidic environment of the lysosome, adhesion when expressed on the cell surface (plasma membrane), and inter- and intracellular signal transduction. (abcam.com)
  • In addition, the involvement of Ca2+ transients in the invasion mechanism of the parasite Trypanosoma cruzi, which occurs by fusion of lysosomes with the plasma membrane, suggested that lysosome exocytosis might be a generalized process present in most cell types. (nih.gov)
  • Here we demonstrate that elevation in the intracellular free Ca2+ concentration of normal rat kidney (NRK) fibroblasts induces fusion of lysosomes with the plasma membrane. (nih.gov)
  • Lysosomes are the terminal compartments in the endocytic pathway, though they display highly dynamic behaviors, fusing with each other and with late endosomes in the endocytic pathway, and with the plasma membrane during regulated exocytosis and for wound repair. (g3journal.org)
  • Subcellular fractionation experiments confirmed that cathepsin B and L activity was increased in the cytosol, and in vitro experiments with isolated lysosomes showed that the lysosomes from glands undergoing involution had increased permeability compared with lysosomes from glands of lactating mice. (sciencemag.org)
  • At pH 4.8, the interior of the lysosomes is acidic compared to the slightly alkaline cytosol (pH 7.2). (medicalxpress.com)
  • The lysosome maintains this pH differential by pumping protons (H+ ions) from the cytosol across the membrane via proton pumps and chloride ion channels. (medicalxpress.com)
  • The lysosomal membrane protects the cytosol, and therefore the rest of the cell, from the degradative enzymes within the lysosome. (medicalxpress.com)
  • It became clear that this enzyme from the cell fraction came from membranous fractions, which were definitely cell organelles, and in 1955 De Duve named them "lysosomes" to reflect their digestive properties. (wikipedia.org)
  • The membrane around a lysosome allows the digestive enzymes to work at the 4.5 pH they require. (medicalxpress.com)
  • Lysosomes fuse with vacuoles to digest their contents. (dictionary.com)
  • Lysosomes fuse with vacuoles and dispense their enzymes into the vacuoles, digesting their contents. (medicalxpress.com)
  • In previous studies, JHU researchers demonstrated that 6-O-glucosamine compounds could be used for biosynthetic fluorescence labeling of lysosomes in cell culture and in vivo tumors. (ideaconnection.com)
  • Lysosomes digest foreign materials and food, explains a Georgia State University website. (reference.com)
  • Lysosomes digest materials taken into the cell and recycle intracellular materials. (wikipedia.org)
  • Lysosomes digest particles by fusing with them and dissolving them in a solution of enzymes. (reference.com)
  • Lysosomes digest excess or worn-out organelles, food particles, and engulf viruses or bacteria. (medicalxpress.com)
  • While lysosomes digest some materials in this process, it is actually accomplished through programmed cell death, called apoptosis . (thefullwiki.org)
  • Lysosomes hold a variety of enzymes that digest or breakdown complex molecules and pieces of cell. (emaxhealth.com)
  • Since Dr de Duve chose to talk today about peroxysomes rather than lysosomes, it might perhaps add to the Discussion to present some data related to this important function, i. e. the ability of lysosomes to digest foreign macromolecular material. (royalsocietypublishing.org)
  • Enzymes destined for a lysosome are specifically tagged with the molecule mannose 6-phosphate, so that they are properly sorted into acidified vesicles. (wikipedia.org)
  • if destined for lysosome, a phosphate group is added to the mannose = mannose-6-phosphate Lysosome function. (musicaenlamochila.net)
  • A cell contains many lysosomes. (reference.com)
  • Lysosomes contain a variety of enzymes, enabling the cell to break down various biomolecules it engulfs, including peptides, nucleic acids, carbohydrates, and lipids (lysosomal lipase). (wikipedia.org)
  • In this review, we will explore the contributions lysosomes play in inducing cell death, how this is regulated by ROS in cancer, and how lysosomotropic agents might be utilized to treat cancers. (hindawi.com)
  • Lysosomes are the most acidic vesicles within the cell. (hindawi.com)
  • Lysosomes are small vesicles that contain a variety of acidic hydrolase enzymes capable of disposing of biological material within a cell. (reference.com)
  • The enzymes contained within a lysosome are strong enough to kill the host cell if not contained within the lysosome's membrane. (reference.com)
  • A cell may contain hundreds of lysosomes. (reference.com)
  • A lysosome is a cell organelle . (wikipedia.org)
  • The study, which will be published August 7 in The Journal of Cell Biology (JCB) , suggests that developing ways to restore lysosome transport could represent a new therapeutic approach to treating the neurodegenerative disorder. (eurekalert.org)
  • In neurons, lysosomes are thought to "mature" as they are transported from the ends of axons to the neuronal cell body, gradually acquiring the ability to degrade their cargo. (eurekalert.org)
  • Lysosome-related organelles occur in specific cell types and fulfil specialised functions e.g. melanosomes which synthesise and store pigments in higher eukaryotes. (ebi.ac.uk)
  • Lysosome s, or what happens when the cell needs to degrade something? (coursehero.com)
  • Brand: Cell Signaling Technology Category: Activators & Inhibitors Lysosome inhibition sensitizes pancreatic cancer to https://www.pnas.org/content/116/14/6842 Apr 02, 2019 · These tumors rely on lysosome-dependent recycling pathways to generate substrates for metabolism, which are inhibited by chloroquine (CQ) and its derivatives. (musicaenlamochila.net)
  • In this review, we have examined the current literature on involvement of lysosomes in induction of programed cell death and have provided an extensive list of therapeutic approaches that can modulate cell death. (wingsforlife.com)
  • Lysosomes are organelles that contain acid hydrolase enzymes, such that materials that are taken up by lysosomes can be degraded into their basic components, and these components can be reused by the cell. (varsitytutors.com)
  • The membrane of the lysosome is selectively permeable due to these types of transporters, and protects the rest of the cell from the very acidic environment. (varsitytutors.com)
  • We didn't know whether these accumulations of lysosomes represented a beneficial response of neurons to the amyloid plaque disease pathology or whether they were somehow deleterious," said Shawn Ferguson, associate professor of cell biology at Yale. (scitechdaily.com)
  • Interference with ESCRT recruitment abolishes lysosome repair and causes otherwise reversible lysosome damage to become cell lethal. (uio.no)
  • We conclude that the cell is equipped with an endogenous mechanism for lysosome repair which protects against lysosomal damage‐induced cell death but which also provides a potential advantage for intracellular pathogens. (uio.no)
  • NRK cell lysosomes were loaded with BSA-gold, and then treated with 10 μM ionomycin for different periods of time. (nih.gov)
  • Our results suggest a potential for delivery of pharmacologically active agents into tumor sites by use of the NK-cell secretory lysosome as a carrier. (lu.se)
  • Uneven distribution of lysosomes, the structures that break down unneeded or worn-out cell parts, can impair the shape and function of neurons in rats, according to a study led by researchers at the National Institutes of Health. (nih.gov)
  • Scientists now know that lysosomes are important for immunity, cell repair, cell migration, and cancer progression, among other functions. (nih.gov)
  • Unexpectedly, the scientists discovered that NFYB-1 steers the activity of mitochondria through another part of the cell called the lysosome, a place where basic molecules are broken down and recycled as nutrients. (longecity.org)
  • SiR700-lysosome is fluorogenic, cell permeable and highly specific for lysosomes. (cytoskeleton.com)
  • Lysosomes are spherical organelles that contain enzymes (acid hydrolases ). (thefullwiki.org)
  • New research from Yale University shows that increased lysosomes in neural projections in a mouse model of Alzheimer's greatly accelerated formation of amyloid plaques. (scitechdaily.com)
  • In the brains of mice with Alzheimer's disease, decreased levels of JIP3 (right) induce the formation of larger amyloid plaques (red) and increased numbers of swollen axons filled with lysosomes. (eurekalert.org)
  • The lysosomes that get stuck and accumulate inside the axonal swellings associated with amyloid plaques fail to properly mature, but how these lysosomes contribute to the development of Alzheimer's disease is unclear. (eurekalert.org)
  • Collectively, our results indicate that the axonal accumulations of lysosomes at amyloid plaques are not innocent bystanders but rather are important contributors to APP processing and amyloid plaque growth," Ferguson says. (eurekalert.org)
  • So why do researchers find so many lysosomes within the neuronal projections surrounding amyloid plaques, a hallmark of Alzheimer's Disease brain pathology? (scitechdaily.com)
  • They found that the additional lysosomes greatly accelerated formation of amyloid plaques. (scitechdaily.com)
  • JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. (scitechdaily.com)
  • Lysosome pH regulates the large stores of calcium in lysosomes. (babraham.ac.uk)
  • PAYWALLED__Subcellular chatter regulates longevity: Lysosome to mitochondria communication. (longecity.org)
  • This review provides an update on the lysosome signaling pathway-mediated Leishmania intracellular development. (frontiersin.org)
  • Mutations in car and dor cause severe defects in intracellular trafficking to the lysosome and defects in eye color ( 8 ). (pubmedcentralcanada.ca)
  • The fusion of lysosomes to phagosomes was observed under high voltage electron microscopy, in 4μm thick rat retinal sections with the aid of acid phosphatase cytochemistry. (nii.ac.jp)
  • A lysosome formed by the combination of a primary lysosome and a phagosome or pinosome and in which lysis takes place through the activity of hydrolytic enzymes. (thefreedictionary.com)
  • The intent in initiating this volume was to bring together a series of essays which would define our present understanding of the endosome and lysosome and their interrelationship. (beck-shop.de)
  • Shawn Ferguson and colleagues at Yale University School of Medicine investigated this possibility by impeding the transport of lysosomes in mouse neurons. (eurekalert.org)
  • BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon. (nih.gov)
  • The in vivo data presented in this report support further the hypothesis, heretofore based on in vitro data, that anti-inflammatory drugs inhibit the extrusion of enzymes from lysosomes. (aspetjournals.org)
  • Our understanding of endosomes and lysosomes has undergone a molecular revolution over the last decade. (beck-shop.de)
  • In this volume current molecular knowledge concerning the function and relationship of endosomes and lysosomes is presented. (beck-shop.de)
  • The dynamic nature of the relationship between endosomes and lysosomes is the unifying focus of the genetic, biochemical, microscopic, and molecular biological approaches described in the chapters which follow. (beck-shop.de)
  • Bafilomycin A1 and chloroquine are compounds that neutralize the pH in lysosomes and endosomes by two distinct mechanisms and as a result, block trafficking between late endosomes and lysosomes. (aacrjournals.org)
  • Ferguson and colleagues investigated how neurons control distribution of lysosomes and used the knowledge to increase lysosomes in neural projections in a mouse model of Alzheimer's. (scitechdaily.com)
  • BNIP3, but not the transmembrane deletion variant, interacted with LC3 and colocalized with mitochondria and lysosomes. (nih.gov)
  • [4] [5] Enzymes of the lysosomes are synthesised in the rough endoplasmic reticulum . (wikipedia.org)
  • Open thyroid follicles were used to prepared a crude particulate fraction, which contained lysosomes, mitochondria and endoplasmic reticulum. (portlandpress.com)
  • Lysosomes are membrane-enclosed vesicles that contain at least 60 hydrolases within an acidic environment. (hindawi.com)
  • Nevertheless the.Drake, Paul D. Chloroquine and hydroxychloroquine are weak bases, which accumulate in the acidic environment of lysosomes and raise intra-lysosomal pH levels, with the resultant decreased ability of macrophages to process antigens.2,4 Moreover, they decrease the lysosomal size and possibly inhibit their function as well, hence exerting anti-inflammatory effects.2. (musicaenlamochila.net)
  • What type of membrane component is likely responsible for maintaining the acidic environment within the lysosome? (varsitytutors.com)
  • The endocytic marker alpha 2 macroglobulin-gold entered the structure at 37 degrees C, but not at 20 degrees C. With prolonged chase, most of the marker was transported from the structure into lysosomes. (nih.gov)
  • We propose that the MPR/lgp-enriched structure is a specialized endosome (prelysosome) that serves as an intermediate compartment into which endocytic vesicles discharge their contents, and where lysosomal enzymes are released from the MPR and packaged along with newly synthesized lysosomal glycoproteins into lysosomes. (nih.gov)
  • Lysosomes are considered to be a terminal degradative compartment of the endocytic pathway, into which transport is mostly unidirectional. (nih.gov)
  • Lysosomes are dynamic structures that undergo cycles of fusion and reformation with endocytic, phagocytic, and autophagic organelles. (g3journal.org)
  • The development of novel fluorescent probes for selective detection of endogenous hydrogen sulfide (H 2 S) in lysosomes is imperative for elucidating its functions associated with diseases. (rsc.org)
  • To solve this problem, we present the aggregation induced emission dots ( AIED ) for selective visualization of endogenous H 2 S in lysosomes via a simple co-precipitation method. (rsc.org)
  • A soluble sTNFR1 form was generated in the secretory lysosome by endogenous proteolytic activity. (lu.se)
  • Lysosomes are also important storage compartments for metal ions and nutrients. (wingsforlife.com)
  • In this study, we used a forward genetic screen in Caenorhabditis elegans to identify six regulators of lysosome biology. (g3journal.org)
  • We investigated the uptake of imipramine (IMP) in highly purified lysosomes from rat liver and its inhibition by a variety of basic drugs in vitro. (aspetjournals.org)
  • Using a staining method for acid phosphatase, de Duve and Novikoff confirmed the location of the hydrolytic enzymes of lysosomes using light and electron microscopic studies. (wikipedia.org)
  • According to new research, in Alzheimer's patients, lysosomes lack the ability to perform their job correctly. (neurosciencenews.com)
  • Fusion of a lysosome with the isolation membrane to form the autolysosome is the penultimate step of the autophagic pathway. (thermofisher.com)
  • The results show that the uptake of multivalent ligands follows the normal pathway of receptor-mediated endocytosis: internalization in clathrin-coated pits and coated vesicles, delivery to endosomes, and finally to acid hydrolase-rich lysosomes. (rupress.org)
  • Cathepsin B, H, L and D activities in liver lysosomes were compared between species. (portlandpress.com)
  • A variety of steroidal and nonsteroidal anti-inflammatory drugs and other therapeutic agents were tested for their capacity to alter in vivo the integrity of rat liver lysosomes. (aspetjournals.org)
  • The integrity of liver lysosomes was assessed by determining their relative mechanical and osmotic fragility. (aspetjournals.org)
  • The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. (rupress.org)
  • The capacity of L. pneumophila to inhibit phagosome-lysosome fusion may be a critical mechanism by which the bacterium resists monocyte microbicidal effects. (rupress.org)
  • The resulting sTNFR1-tm-Y was targeted to secretory lysosomes as confirmed by results from biosynthetic radiolabeling in combination with. (lu.se)
  • coronavirus belgique chloroquine lysosome inhibitor mechanism %INSIDE_LINK_36% Coronavirus temperature, coronavirus virginia tech Coronavirus patient zero maatje benassi. (musicaenlamochila.net)
  • 100-fold excess concentration and causes an elevation of chloroquine lysosome function pH due to trapping of H + ions by chloroquine. (musicaenlamochila.net)
  • The uptake of [ 3 H]IMP into lysosomes peaked in less than 20 s, showing little temperature dependency or countertransport phenomena. (aspetjournals.org)
  • However, the uptake of [ 3 H]IMP in lysosomes was approximately 140-fold higher than the value expected from the pH-partition theory. (aspetjournals.org)
  • We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. (uzh.ch)
  • However, BNIP3 did not target to lysosomes by subcellular fractionation, provoke lysosome permeabilization or alter lysosome pH. (nih.gov)
  • Lysosomes accumulate weakly basic amine-containing drugs (i.e., lysosomotropic amines) through an ion trapping-type mechanism and are capable of disrupting lysosomal structure and function. (ku.edu)
  • The findings suggest that reducing the build-up of lysosomes within neurons might be a novel way to treat dementia, said the researchers. (scitechdaily.com)
  • Researchers led by Juan Bonifacino, Ph.D., of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, studied lysosome transportation in neurons using rats. (nih.gov)