Lysosomes: 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)Lysosome-Associated Membrane Glycoproteins: Ubiquitously expressed integral membrane glycoproteins found in the LYSOSOME.Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Phagosomes: Membrane-bound cytoplasmic vesicles formed by invagination of phagocytized material. They fuse with lysosomes to form phagolysosomes in which the hydrolytic enzymes of the lysosome digest the phagocytized material.Cathepsin D: An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).Autophagy: The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.Lysosomal-Associated Membrane Protein 2: An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. Loss of expression of lysosomal-associated membrane protein 2 is associated with GLYCOGEN STORAGE DISEASE TYPE IIB.Microscopy, Electron: 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.Cathepsins: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.Chediak-Higashi Syndrome: A form of phagocyte bactericidal dysfunction characterized by unusual oculocutaneous albinism, high incidence of lymphoreticular neoplasms, and recurrent pyogenic infections. In many cell types, abnormal lysosomes are present leading to defective pigment distribution and abnormal neutrophil functions. The disease is transmitted by autosomal recessive inheritance and a similar disorder occurs in the beige mouse, the Aleutian mink, and albino Hereford cattle.beta-N-Acetylhexosaminidases: A hexosaminidase specific for non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. It acts on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES. Two specific mammalian isoenzymes of beta-N-acetylhexoaminidase are referred to as HEXOSAMINIDASE A and HEXOSAMINIDASE B. Deficiency of the type A isoenzyme causes TAY-SACHS DISEASE, while deficiency of both A and B isozymes causes SANDHOFF DISEASE. The enzyme has also been used as a tumor marker to distinguish between malignant and benign disease.Receptor, IGF Type 2: 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.Cell Fractionation: Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Mannosephosphates: Phosphoric acid esters of mannose.Organelles: 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.GlucuronidaseMucolipidoses: A group of inherited metabolic diseases characterized by the accumulation of excessive amounts of acid mucopolysaccharides, sphingolipids, and/or glycolipids in visceral and mesenchymal cells. Abnormal amounts of sphingolipids or glycolipids are present in neural tissue. INTELLECTUAL DISABILITY and skeletal changes, most notably dysostosis multiplex, occur frequently. (From Joynt, Clinical Neurology, 1992, Ch56, pp36-7)Organoids: An organization of cells into an organ-like structure. Organoids can be generated in culture. They are also found in certain neoplasms.Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates.Cathepsin B: A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Compartmentation: A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Androstenes: Unsaturated derivatives of the steroid androstane containing at least one double bond at any site in any of the rings.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.Arylsulfatases: Enzymes that catalyze the hydrolysis of a phenol sulfate to yield a phenol and sulfate. Arylsulfatase A, B, and C have been separated. A deficiency of arylsulfatases is one of the causes of metachromatic leukodystrophy (LEUKODYSTROPHY, METACHROMATIC). EC 3.1.6.1.Histocytochemistry: Study of intracellular distribution of chemicals, reaction sites, enzymes, etc., by means of staining reactions, radioactive isotope uptake, selective metal distribution in electron microscopy, or other methods.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Acetylglucosaminidase: A beta-N-Acetylhexosaminidase that catalyzes the hydrolysis of terminal, non-reducing 2-acetamido-2-deoxy-beta-glucose residues in chitobiose and higher analogs as well as in glycoproteins. Has been used widely in structural studies on bacterial cell walls and in the study of diseases such as MUCOLIPIDOSIS and various inflammatory disorders of muscle and connective tissue.Multivesicular Bodies: Endosomes containing intraluminal vesicles which are formed by the inward budding of the endosome membrane. Multivesicular bodies (MVBs) may fuse with other organelles such as LYSOSOMES or fuse back with the PLASMA MEMBRANE releasing their contents by EXOCYTOSIS. The MVB intraluminal vesicles released into the extracellular environment are known as EXOSOMES.Ammonium Chloride: An acidifying agent that has expectorant and diuretic effects. Also used in etching and batteries and as a flux in electroplating.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology.Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Hexosaminidases: Enzymes that catalyze the hydrolysis of N-acylhexosamine residues in N-acylhexosamides. Hexosaminidases also act on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES.Vesicular Transport Proteins: A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Cathepsin L: A ubiquitously-expressed cysteine protease that plays an enzymatic role in POST-TRANSLATIONAL PROTEIN PROCESSING of proteins within SECRETORY GRANULES.Asialoglycoproteins: Endogenous glycoproteins from which SIALIC ACID has been removed by the action of sialidases. They bind tightly to the ASIALOGLYCOPROTEIN RECEPTOR which is located on hepatocyte plasma membranes. After internalization by adsorptive ENDOCYTOSIS they are delivered to LYSOSOMES for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with HEPATIC CIRRHOSIS or HEPATITIS.Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.Cystinosis: A metabolic disease characterized by the defective transport of CYSTINE across the lysosomal membrane due to mutation of a membrane protein cystinosin. This results in cystine accumulation and crystallization in the cells causing widespread tissue damage. In the KIDNEY, nephropathic cystinosis is a common cause of RENAL FANCONI SYNDROME.Phagocytosis: The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.SulfatasesPepstatins: N-acylated oligopeptides isolated from culture filtrates of Actinomycetes, which act specifically to inhibit acid proteases such as pepsin and renin.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Fetuins: A family of calcium-binding alpha-globulins that are synthesized in the LIVER and play an essential role in maintaining the solubility of CALCIUM in the BLOOD. In addition the fetuins contain aminoterminal cystatin domains and are classified as type 3 cystatins.rab5 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in transport from the cell membrane to early endosomes. This enzyme was formerly listed as EC 3.6.1.47.Adaptor Protein Complex 3: An adaptor protein complex found primarily on perinuclear compartments.Kinetics: The rate dynamics in chemical or physical systems.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Centrifugation, Density Gradient: Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Saposins: A group of four homologous sphingolipid activator proteins that are formed from proteolytic cleavage of a common protein precursor molecule referred to as prosaposin.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Niemann-Pick Diseases: A group of autosomal recessive disorders in which harmful quantities of lipids accumulate in the viscera and the central nervous system. They can be caused by deficiencies of enzyme activities (SPHINGOMYELIN PHOSPHODIESTERASE) or defects in intracellular transport, resulting in the accumulation of SPHINGOMYELINS and CHOLESTEROL. There are various subtypes based on their clinical and genetic differences.Endosomal Sorting Complexes Required for Transport: A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Vacuolar Proton-Translocating ATPases: Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.Dextrans: 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.Proteolysis: Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.Cathepsin C: A papain-like cysteine protease that has specificity for amino terminal dipeptides. The enzyme plays a role in the activation of several pro-inflammatory serine proteases by removal of their aminoterminal inhibitory dipeptides. Genetic mutations that cause loss of cathepsin C activity in humans are associated with PAPILLON-LEFEVRE DISEASE.Molecular Sequence Data: 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.Melanosomes: Melanin-containing organelles found in melanocytes and melanophores.Amino Acid Sequence: 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.Transport Vesicles: Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations.Monensin: An antiprotozoal agent produced by Streptomyces cinnamonensis. It exerts its effect during the development of first-generation trophozoites into first-generation schizonts within the intestinal epithelial cells. It does not interfere with hosts' development of acquired immunity to the majority of coccidial species. Monensin is a sodium and proton selective ionophore and is widely used as such in biochemical studies.Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism.Clathrin: The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.

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)

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 ...
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 ...
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 ...
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 ...
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 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). ...
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 ...
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 ...
Cellular organelles allow the localized regulation of specialized processes. Under certain conditions, such as increased growth, organelles may be required to alter their function. Coordinated regulation of the gene networks required for mitochondrial and endoplasmic reticulum function has been observed. Now, Sardiello et al. (p. 473; published online 25 June) have discovered a gene network regulating the lysosome, the major organelle involved in the degradation of internalized macromolecules. Many lysosomal genes were regulated by a single transcription factor, TFEB. TFEB itself can be activated when the lysosome malfunctions and can regulate both the abundance of lysosomes found in the cell, as well as the ability to degrade complex molecules, including a mutant protein that accumulates in patients with Huntingtons disease. These results may have implications for the treatment of human lysosomal storage disorders, which are characterized by the aberrant accumulation of macromolecules causing ...
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.
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 ...
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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Familial Alzheimers disease (FAD) is associated with mutations in the gene encoding presenilin 1 (PS1), a component of the γ-secretase complex, which cleaves type I membrane proteins, such as amyloid precursor protein. Mutations in PS1 are also associated with defects in autophagy in neurons; however, the mechanism involved is unknown. Lee et al. found that autophagy was impaired in blastocysts from PS1 knockout (PS1 KO) mice compared with that in wild-type (WT) blastocysts, which led to the accumulation of autophagic vacuoles (AVs) in PS1 KO cells. Fusion of autophagosomes with lysosomes was normal in PS1 KO cells, but degradation of autolysosomal components was blocked. The pH of lysosomes in PS1 KO cells was higher than that in lysosomes from WT cells, which was associated with the absence of the vacuolar ATPase Voa1 subunit (a proton pump that acidifies lysosomes) from the PS1 KO lysosomes. In WT cells, PS1 associated with Voa1 in the endoplasmic reticulum (ER) and was required for the ...
Within APCs, ubiquitination regulates the trafficking of immune modulators such as MHC class II and CD86 (B7.2) molecules. MARCH1 (membrane-associated RING-CH), a newly identified ubiquitin E3 ligase expressed in APCs, ubiquitinates MHC class II, thereby reducing its surface expression. Following LPS-induced maturation of dendritic cells, MARCH1 mRNA is down-regulated and MHC class II is redistributed to the cell surface from endosomal compartments. Here, we show that MARCH1 expression is also regulated at the posttranscriptional level. In primary dendritic cell and APC cell lines of murine origin, MARCH1 had a half-life of ,30 min. MARCH1 degradation appears to occur partly in lysosomes, since inhibiting lysosomal activity stabilized MARCH1. Similar stabilization was observed when MARCH1-expressing cells were treated with cysteine protease inhibitors. Mutational analyses of MARCH1 defined discrete domains required for destabilization, proper localization, and functional interaction with ...
Cellular Screening Methods for the Study of Nanoparticle- Induced Lysosomal Damage. By Eleonore Fröhlich. Nanoparticles (NPs) are included in many products of daily life and present in the environment. Due to the potential of NPs to improve quality and stability of consumer and health and medical products, it is expected that the exposure of humans to engineered NPs will rather increase than decrease in the future. Although NPs did not act acutely cytotoxic on these concentrations, they may cause adverse effects upon chronic exposure. Cytotoxicity testing in long-term cultures and analysis of organelle function could identify such effects. Cells take up NPs mainly via active mechanisms, and these routes deliver their payload predominantly to lysosomes. Acute exposure of cells to NPs can have adverse effects on lysosome morphology and function, but lysosomes are also potential targets for accumulation. The chapter explains the role of lysosomes and describes techniques for labeling and ...
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How are lysosomal degradation pathways spatially organized in the complex landscape of a neuron? Cheng et al. (2018. J Cell Biol. https://doi.org/10.1083/jcb.201711083) and Yap et ...
There is delayed but increased FA oxidation in 6-week apoB ASO-treated livers. Lipolysis of lipids within autolysosomes, with delivery of their FAs to mitochondria, could lead to oxidation that would compensate for the lack of secretion of VLDL, but our studies of FA oxidation in primary hepatocytes had not demonstrated differences between cells from control ASO- and apoB ASO-treated mice (Figure 2G). We considered the possibility that the 2-hour labeling-collection protocol used for those studies was too short to observe the oxidation of 14C OA which, after incorporation into lipids in the ER membrane, would have to move to the lumen, then be incorporated into autophagosomes that would have to fuse to lysosomes before the lipids could be hydrolyzed to allow released 14C OA to finally be oxidized by mitochondria. This schema is supported by published data demonstrating that the peak fusion of autophagosomes with lysosomes can occur as late as 16 hours after stimulation of autophagy (23, ...
Detail záznamu - The 2,2,4,4,5,5-hexachlorobiphenyl-enhanced degradation of connexin 43 involves both proteasomal and lysosomal activities - Detail záznamu - Knihovna Akademie věd České republiky
Ion-dependent channels and transporters have been identified in lysosomes, including the V-ATPase H+ pump and transient receptor potential mucolipin channels (TRPMLs), the principle Ca2+ release channels in the lysosome, but much less is understood about the roles of Na+ and K+ in lysosomal physiology. Wang et al. describe a voltage-sensitive, Ca2+-activated K+ current in the lysosome (LysoKVCa) and show that LysoKVCa regulates lysosomal membrane potential and refilling of lysosomal Ca2+ stores. ...
Cation channels present in the ES incorporate users with the TRP (transient receptor likely) channel superfamily, specifically TRPML channels (mucolipins) and also two-pore channels (TPCs). In recent reports, these channels are located to Enjoy vital roles in endolysosomal trafficking, lysosomal exocytosis, and autophagy. Mutation or reduction of those channel proteins can impact several endolysosomal trafficking pathways. A task for TPCs in cancer cell migration and metastasis, connected to distinctive defects in endolysosomal trafficking for example integrin trafficking, has actually been not long ago set up. With this evaluate, we give an summary to the operate of lysosomes in cancer with a selected deal with the roles which TPCs and TRPML channels Enjoy from the ES And the way This may affect cancer cells. Full ...
While both snapin‐S50D and snapin‐L99K mutants induced SV accumulation at presynaptic boutons (Fig 3A and B) by disrupting the retrograde transport of SV cargoes along the endolysosomal pathway (Fig 2B and C), only snapin‐L99K reduced the releasable pool size (Fig 5A-C). In view of the biochemical data (Supplementary Fig S3A), this raises the possibility that dysbindin/BLOC‐1‐dependent function (Route 2) is required for maintaining the releasable pool size. Our previous study revealed desynchronized EPSCs in snapin−/− neuronal cultures (Pan et al, 2009), reminiscent of manipulations that decrease the physical coupling of SVs with voltage‐dependent Ca2+ channels (Mochida et al, 1996). Such deficits can be readily rescued by raising the extracellular Ca2+ concentration [Ca2+]ext (Pan et al, 2009). Therefore, snapin represents an attractive candidate in facilitating the positional priming of SVs toward Ca2+ entry sites (Wadel et al, 2007), thus influencing the Ca2+ sensitivity of ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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Association of hVam6p with clusters of lysosomes and late endosomes. HeLa cells were transiently transfected with HA-hVam6p and processed for immunoelectron m
TY - JOUR. T1 - Carbohydrate Processing Enzyme of the Lysosome: Diseases Caused by Missfolded Mutants and Sugar Mimetics as Correcting Pharmacological Chaperones. AU - Stütz, Arnold. AU - Wrodnigg, Tanja. PY - 2016. Y1 - 2016. M3 - Article. VL - 73. SP - 225. EP - 302. JO - Advances in Carbohydrate Chemistry and Biochemistry. JF - Advances in Carbohydrate Chemistry and Biochemistry. SN - 0065-2318. ER - ...
Lysosomes and MVBs in the bnch mutant visual system. (A-D) TEM sections through bnch mutant eyes. (A) Multilammellar onion-like structure with morphologically
Lysosomes provide such an environment by maintaining a pH of 5.0 inside of the organelle. If a lysosome were to rupture, the ... However, if numerous lysosomes leaked the cell could be destroyed from autodigestion. Lysosomes carry out intracellular ... The main functions of a lysosome are to process molecules taken in by the cell and to recycle worn out cell parts. The enzymes ... The lysosome engulfs another organelle and uses its enzymes to take apart the ingested material. The resulting organic monomers ...
Mutations of synuclien alleles lead to lysosome pH increase and hydrolase inhibition. As a result, lysosomes degradative ... Within the lysosome, the contents of the autophagosome are degraded via acidic lysosomal hydrolases. Microautophagy, on the ... In January 1962 they reported an increased number of lysosomes in rat liver cells after the addition of glucagon, and that some ... This was the first time the fact that lysosomes were established as the sites of intracellular autophagy. A new era of ...
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 ...
Lysosomes, Plasma membrane ----> Endosomes (receptor-mediated endocytosis) Membrane transport protein Wikipedia:MeSH_D12.776# ...
Roy, A.B. (1976). "Sulphatases, lysosomes and disease". Aust. J. Exp. Biol. Med. Sci. 54 (2): 111-135. doi:10.1038/icb.1976.13 ...
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 ... Winckler, J. Vital staining of lysosomes and other cell organelles of the rat with neutral Red. Prog. Histochem. Cytochem. 6, 1 ... Live cells incorporate neutral red into their lysosomes. As cells begin to die, their ability to incorporate neutral red ...
The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome. BioGPS analysis for ... Schroder BA, Wrocklage C, Hasilik A, Saftig P (19 October 2010). "The Proteome of Lysosomes". Proteomics. 10 (22): 4053-4076. ... with the N-terminus of the protein being within the lysosome and the C-terminus located in the cytosol. Post-translational ...
... 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. Retrieved 12 November 2017. "Re: Are there eukaryotic cells without mitochondria ... and single membrane structures such as lysosomes. Mitochondria are proposed to come from the endosymbiosis of an aerobic ...
... lysosomes, and peroxisomes; Microsomes (vesicles of disrupted endoplasmic reticulum); and Ribosomes and cytosol. High g-force ...
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 ...
Lysosomes are involved in cellular digestion. Food can be taken from outside the cell into food vacuoles by a process called ... 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, ...
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 ...
"Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes ...
... 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 ... They control actin polymerisation which is required for the phagosome to fuse with endosomes and lysosomes. Other non- ... Roy, Craig R.; Kagan, Jonathan C. (1 January 2013). "Evasion of Phagosome Lysosome Fusion and Establishment of a Replicative ...
They are subsequently degraded in lysosomes. The remaining free amino acids are transported across the basolateral membrane by ...
Organelles and bits of cytoplasm are sequestered and targeted for degradation by the lysosome for hydrolytic digestion by a ... Mitochondrial fragments had been seen in liver lysosomes as early as 1962, and a 1977 report suggested that "mitochondria ... This turnover process consists of the sequestration and hydrolytic degradation by the lysosome, a process also known as ... 8: 3-5. doi:10.1089/rej.2005.8.3. Ashford, TP; Porter, KR (1962). "Cytoplasmic components of hepatic cell lysosomes". The ...
The lancet sperm sometimes contain many lysosomes. Some Sculpin may be sperm heteromorphic. Their ejaculates appear to contain ...
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 ... The disease is characterised by large lysosome vesicles in phagocytes (neutrophils), which thus have poor bactericidal function ... As a result of disordered intracellular trafficking there is impaired lysosome degranulation with phagosomes, so phagocytosed ...
... RNAi also disperse endosomes and lysosomes. Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for ...
The lysosome, therefore, is not able to break down components the way it should. This inability is associated with the onset of ... This increase in signaling leads to an increase in size of the lysosomes due to the increased rate and amount of fusion. ... The TPC mechanism once again allows the influx of calcium for the fusion of the endosomes and lysosomes (where LDL is degraded ... Therefore, when TPCs are not functioning, the Ebolavirus cannot escape before the fusion of the endosome with the lysosome. In ...
IGF-II will then be targeted to the lysosome where it will be degraded. This regulates the level of free IGF-II in the body. ... This ensures that all harmful lysosomal enzymes will be targeted to the lysosome. CI-MPR Mice lacking the CI-MPR die at day 15 ... MPRs are not found in the lysosomes; they cycle mainly between the trans-Golgi network and endosomes. The CI-MPR is also ... Instead of being sent to the lysosome, they were being secreted. Furthermore, these mis-targeted enzymes were found to not be ...
It is proposed that the role of SK1 located near or in the lysosome is to 'trap' Sph via phosphorylation. It is important to ... Sphingosine (Sph) is formed by the action of ceramidase (CDase) enzymes on ceramide in the lysosome. Sph can also be formed in ... However, its positive charge favors partitioning in lysosomes. ... Sph may come out of the lysosome and move to the ER without the ... cathepsin D has been proposed as the main target for ceramide formed in organelles called lysosomes, making lysosomal acidic ...
Cystinosis is an inborn metabolic error characterized by the abnormal transport of cystine, an amino acid, out of the lysosomes ...
Given this central importance of lysosomes, it is striking that little is known about how lysosomes are formed, the process we ... Lysosomes also mediate some cell death pathways and play crucial roles in wound repair. Indeed, lysosomal dysfunction is a ... Lysosomes are membrane-bound organelles that serve as the major degradative compartments for endocytic, phagocytic, and ... To elucidate mechanisms of lysosome biogenesis.. *To decipher the basis for lysosomal dysfunction and cell death in the ...
All granule bearing cells are affected resulting in giant, yet defective lysosomes, melanosomes, platelet dense granules, and T ... The pathologic hallmark of CHS is the development of large intracellular granules and abnormal lysosome trafficking. The ... a gene important in the trafficking of proteins to the lysosome. Clinically, HPS is characterized by albinism, a bleeding ... fusion of intracellular granules and defective membrane targeting of many of the proteins present in secretory lysosomes. ...
Protein found in the lysosome, a membrane-limited organelle present in all eukaryotic cells, which contains a large number of ...
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 ...
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 size of lysosomes varies from 0.1 μm to 1.2 μm. With a pH ranging from 4.5 to 5.0, the interior of the lysosomes is acidic ... Lysosomes are known to contain more than 60 different enzymes. Enzymes of the lysosomes are synthesised in the rough ... Vacuoles do not have catabolic activity and do not undergo exocytosis as lysosomes do. The word lysosome (/ˈlaɪsoʊsoʊm/, / ... Lüllmznn-Rauch R (2005). "History and Morphology of Lysosome". In Zaftig P. Lysosomes (Online-Ausg. 1 ed.). Georgetown, Tex.: ...
Lysosomes - By: Scott Jakobsze by Scott Jakobsze , This newsletter was created with Smore, an online tool for creating ...
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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Lysosome-associated membrane glycoproteins (lamp) 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 ...
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/ ...
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The results confirm and extend the conclusion, derived from previous investigations on normal animals, that the lysosomes of ...
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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 ...
Starvation activates a transcriptional program controlling autophagosome formation, lysosome fusion, and substrate degradation. ... Starvation activates a transcriptional program controlling autophagosome formation, lysosome fusion, and substrate degradation. ... autophagosome-lysosome fusion, and substrate degradation. The transcription factor EB (TFEB), a master gene for lysosomal ... autophagosomes and lysosomes, whose synergy is required for an efficient autophagic process. During starvation, cells activated ...
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 ...
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. ...
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. ...
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 ...
  • Cystinosis is an inborn metabolic error characterized by the abnormal transport of cystine, an amino acid, out of the lysosomes. (science20.com)
  • Lysosomes were discovered by the Belgian cytologist Christian de Duve in the 1960s. (medicalxpress.com)
  • The lysosomes also act as the waste disposal system of the cell by digesting unwanted materials in the cytoplasm , both from outside the cell and obsolete components inside 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)
  • A network of tubular lysosomes extends through the cytoplasm of J774.2 macrophages and phorbol ester-treated mouse peritoneal macrophages. (rupress.org)
  • 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)
  • Lysosomes are considered to be a terminal degradative compartment of the endocytic pathway, into which transport is mostly unidirectional. (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)
  • 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)
  • It became clear that this enzyme from the cell fraction came from a membranous fractions, which were definitely cell organelles, and in 1955 De Duve named them "lysosomes" to reflect their digestive properties. (wikipedia.org)
  • EAD1 causes dissociation of mTOR from lysosomes and increases mTOR's perinuclear versus cytoplasmic localization, changes previously shown to inactivate mTORC1. (aspetjournals.org)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Following the initial discovery that localisation of the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), to the lysosome was essential for mTORC1 activation, the field has rapidly expanded to reveal the role of the lysosome as a platform permitting the co-ordination of several homeostatic signalling pathways. (portlandpress.com)
  • 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 s, or what happens when the cell needs to degrade something? (coursehero.com)
  • 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)
  • 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)
  • 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)