Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
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.
A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.
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)
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.
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.
A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.
A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in recycling of proteins such as cell surface receptors from early endosomes to the cell surface. This enzyme was formerly listed as EC 3.6.1.47.
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.
An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states.
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.
Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.
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.
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)
A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
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.
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.
A large family of phosphatidylinositol phosphate-binding proteins that are involved in mediating intracellular transport and sorting of proteins via a variety of endocytic pathways.
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.
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.
Ubiquitously expressed integral membrane glycoproteins found in the LYSOSOME.
Vesicles formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein CLATHRIN. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as ENDOSOMES.
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.
Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.
Established cell cultures that have the potential to propagate indefinitely.
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.
A clathrin adaptor protein complex primarily involved in clathrin-related transport at the TRANS-GOLGI NETWORK.
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.
A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.
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.
GLYCEROL esterified with a single acyl (FATTY ACIDS) chain.
A subfamily of Q-SNARE PROTEINS which occupy the same position as syntaxin 1A in the SNARE complex and which also are most similar to syntaxin 1A in their AMINO ACID SEQUENCE. This subfamily is also known as the syntaxins, although a few so called syntaxins are Qc-SNARES.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
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.
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.
MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47
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.
Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.
A family of large adaptin protein subunits of approximately 90 KDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 1.
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)
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.
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)
Transport proteins that carry specific substances in the blood or across cell membranes.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.
Specialized regions of the cell membrane composed of pits coated with a bristle covering made of the protein CLATHRIN. These pits are the entry route for macromolecules bound by cell surface receptors. The pits are then internalized into the cytoplasm to form the COATED VESICLES.
SNARE proteins where the central amino acid residue of the SNARE motif is an ARGININE. They are classified separately from the Q-SNARE PROTEINS where the central amino acid residue of the SNARE motif is a GLUTAMINE. This subfamily contains the vesicle associated membrane proteins (VAMPs) based on similarity to the prototype for the R-SNAREs, VAMP2 (synaptobrevin 2).
The entering of cells by viruses following VIRUS ATTACHMENT. This is achieved by ENDOCYTOSIS, by direct MEMBRANE FUSION of the viral membrane with the CELL MEMBRANE, or by translocation of the whole virus across the cell membrane.
Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.
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.
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).
Unsaturated derivatives of the steroid androstane containing at least one double bond at any site in any of the rings.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
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.
Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
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.
An adaptor protein complex found primarily on perinuclear compartments.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A member of the vesicle associated membrane protein family. It has a broad tissue distribution and is involved in MEMBRANE FUSION events of the endocytic pathways.
A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.
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.
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.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.
Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.
Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains.
A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.
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.
Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.
An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. In PLATELETS and T-LYMPHOCYTES it may play a role in the cellular degranulation process.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.
Glycoproteins found on the membrane or surface of cells.
A member of the annexin family that is a substrate for a tyrosine kinase, ONCOGENE PROTEIN PP60(V-SRC). Annexin A2 occurs as a 36-KDa monomer and in a 90-KDa complex containing two subunits of annexin A2 and two subunits of S100 FAMILY PROTEIN P11. The monomeric form of annexin A2 was formerly referred to as calpactin I heavy chain.
Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
A family of multisubunit cytoskeletal motor proteins that use the energy of ATP hydrolysis to power a variety of cellular functions. Dyneins fall into two major classes based upon structural and functional criteria.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
A superfamily of small proteins which are involved in the MEMBRANE FUSION events, intracellular protein trafficking and secretory processes. They share a homologous SNARE motif. The SNARE proteins are divided into subfamilies: QA-SNARES; QB-SNARES; QC-SNARES; and R-SNARES. The formation of a SNARE complex (composed of one each of the four different types SNARE domains (Qa, Qb, Qc, and R)) mediates MEMBRANE FUSION. Following membrane fusion SNARE complexes are dissociated by the NSFs (N-ETHYLMALEIMIDE-SENSITIVE FACTORS), in conjunction with SOLUBLE NSF ATTACHMENT PROTEIN, i.e., SNAPs (no relation to SNAP 25.)
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
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)
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.
Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
The rate dynamics in chemical or physical systems.
An acidifying agent that has expectorant and diuretic effects. Also used in etching and batteries and as a flux in electroplating.

Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. (1/4632)

The vacuolar protein sorting (VPS) pathway of Saccharomyces cerevisiae mediates transport of vacuolar protein precursors from the late Golgi to the lysosome-like vacuole. Sorting of some vacuolar proteins occurs via a prevacuolar endosomal compartment and mutations in a subset of VPS genes (the class D VPS genes) interfere with the Golgi-to-endosome transport step. Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1]. Another of these proteins, Vac1p/Pep7p/Vps19p, associates with Pep12p and binds phosphatidylinositol 3-phosphate (PI(3)P), the product of the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) [1] [2]. Here, we demonstrate that Vac1p genetically and physically interacts with the activated, GTP-bound form of Vps21p, a Rab GTPase that functions in Golgi-to-endosome transport, and with Vps45p. These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein. We suggest that Vac1p functions as a multivalent adaptor protein that ensures the high fidelity of vesicle docking and fusion by integrating both phosphoinositide (Vps34p) and GTPase (Vps21p) signals, which are essential for Pep12p- and Vps45p-dependent targeting of Golgi-derived vesicles to the prevacuolar endosome.  (+info)

PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. (2/4632)

The Transmembrane 4 Superfamily member, PETA-3/CD151, is ubiquitously expressed by endothelial cells in vivo. In cultured human umbilical vein endothelial cells PETA-3 is present on the plasma membrane and predominantly localises to regions of cell-cell contact. Additionally, this protein is abundant within an intracellular compartment which accounts for up to 66% of the total PETA-3 expressed. Intracellular PETA-3 showed colocalisation with transferrin receptor and CD63 suggesting an endosomal/lysosomal localisation which was supported by immuno-electronmicroscopy studies. Co-immunoprecipitation experiments investigating possible interactions of PETA-3 with other molecules demonstrated associations with several integrin chains including beta1, beta3, beta4, (alpha)2, (alpha)3, (alpha)5, (alpha)6 and provide the first report of Transmembrane 4 Superfamily association with the (alpha)6beta4 integrin. Using 2-colour confocal microscopy, we demonstrated similar localisation of PETA-3 and integrin chains within cytoplasmic vesicles and endothelial cell junctions. In order to assess the functional implications of PETA-3/integrin associations, the effect of anti-PETA-3 antibodies on endothelial function was examined. Anti-PETA-3 mAb inhibited endothelial cell migration and modulated in vitro angiogenesis, but had no detectable effect on neutrophil transendothelial migration. The broad range of integrin associations and the presence of PETA-3 with integrins both on the plasma membrane and within intracellular vesicles, suggests a primary role for PETA-3 in regulating integrin trafficking and/or function.  (+info)

Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network. (3/4632)

SNARE proteins are known to play a role in regulating intracellular protein transport between donor and target membranes. This docking and fusion process involves the interaction of specific vesicle-SNAREs (e.g. VAMP) with specific cognate target-SNAREs (e.g. syntaxin and SNAP-23). Using human SNAP-23 as the bait in a yeast two-hybrid screen of a human B-lymphocyte cDNA library, we have identified the 287-amino-acid SNARE protein syntaxin 11. Like other syntaxin family members, syntaxin 11 binds to the SNARE proteins VAMP and SNAP-23 in vitro and also exists in a complex with SNAP-23 in transfected HeLa cells and in native human B lymphocytes. Unlike other syntaxin family members, no obvious transmembrane domain is present in syntaxin 11. Nevertheless, syntaxin 11 is predominantly membrane-associated and colocalizes with the mannose 6-phosphate receptor on late endosomes and the trans-Golgi network. These data suggest that syntaxin 11 is a SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network in mammalian cells.  (+info)

The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. (4/4632)

The natural resistance associated macrophage protein (Nramp) gene family is composed of two members in mammals, Nramp1 and Nramp2. Nramp1 is expressed primarily in macrophages and mutations at this locus cause susceptibility to infectious diseases. Nramp2 has a much broader range of tissue expression and mutations at Nramp2 result in iron deficiency, indicating a role for Nramp2 in iron metabolism. To get further insight into the function and mechanism of action of Nramp proteins, we have generated isoform specific anti-Nramp1 and anti-Nramp2 antisera. Immunoblotting experiments indicate that Nramp2 is present in a number of cell types, including hemopoietic precursors, and is coexpressed with Nramp1 in primary macrophages and macrophage cell lines. Nramp2 is expressed as a 90-100-kD integral membrane protein extensively modified by glycosylation (>40% of molecular mass). Subcellular localization studies by immunofluorescence and confocal microscopy indicate distinct and nonoverlapping localization for Nramp1 and Nramp2. Nramp1 is expressed in the lysosomal compartment, whereas Nramp2 is not detectable in the lysosomes but is expressed primarily in recycling endosomes and also, to a lower extent, at the plasma membrane, colocalizing with transferrin. These findings suggest that Nramp2 plays a key role in the metabolism of transferrin-bound iron by transporting free Fe2+ across the endosomal membrane and into the cytoplasm.  (+info)

Visualization of receptor-mediated endocytosis in yeast. (5/4632)

We studied the ligand-induced endocytosis of the yeast alpha-factor receptor Ste2p by immuno-electron microscopy. We observed and quantitated time-dependent loss of Ste2p from the plasma membrane of cells exposed to alpha-factor. This ligand-induced internalization of Ste2p was blocked in the well-characterized endocytosis-deficient mutant sac6Delta. We provide evidence that implicates furrow-like invaginations of the plasma membrane as the site of receptor internalization. These invaginations are distinct from the finger-like plasma membrane invaginations within actin cortical patches. Consistent with this, we show that Ste2p is not located within the cortical actin patch before and during receptor-mediated endocytosis. In wild-type cells exposed to alpha-factor we also observed and quantitated a time-dependent accumulation of Ste2p in intracellular, membrane-bound compartments. These compartments have a characteristic electron density but variable shape and size and are often located adjacent to the vacuole. In immuno-electron microscopy experiments these compartments labeled with antibodies directed against the rab5 homologue Ypt51p (Vps21p), the resident vacuolar protease carboxypeptidase Y, and the vacuolar H+-ATPase Vph1p. Using a new double-labeling technique we have colocalized antibodies against Ste2p and carboxypeptidase Y to this compartment, thereby identifying these compartments as prevacuolar late endosomes.  (+info)

Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster. (6/4632)

Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place. A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes, indicating that the accumulation in the TGN reflects a dynamic localization process. The cytosolic domain of furin is necessary and sufficient for TGN localization, and two signals are responsible for retrieval of furin to the TGN. A tyrosine-based (YKGL) motif mediates internalization of furin from the cell surface into endosomes. An acidic cluster that is part of two casein kinase II phosphorylation sites (SDSEEDE) is then responsible for retrieval of furin from endosomes to the TGN. In addition, the acidic EEDE sequence also mediates endocytic activity. Here, we analyzed the sorting of furin in polarized epithelial cells. We show that furin is delivered to the basolateral surface of MDCK cells, from where a significant fraction of the protein can return to the TGN. A phenylalanine-isoleucine motif together with the acidic EEDE cluster is required for basolateral sorting and constitutes a novel signal regulating intracellular traffic of furin.  (+info)

An arrested late endosome-lysosome intermediate aggregate observed in a Chinese hamster ovary cell mutant isolated by novel three-step screening. (7/4632)

Chinese hamster ovary cell mutants defective in the post-uptake degradation of low-density lipoprotein (LDL) in lysosomes were selected from mutagenized cells by novel three-step screening. First, in the presence of LDL, clones sensitive to an inhibitor of the rate-limiting enzyme of the cholesterol biosynthetic pathway, 3-hydroxy-3-methylglutaryl-CoA reductase, were isolated. Second, from the selected clones, those lacking in the degradation of a constituent of a fluorescent LDL were qualitatively screened by microscopy. Third, the clones were further screened by previously established quantitative analytical flow cytometry that detects the early-phase disintegration of LDL by lysosomal acid hydrolases. One of the isolated mutant clones, LEX1 (Lysosome-Endosome X 1), was a recessive mutant, and exhibited a specific disorder in the late endocytic pathway. LEX1 cells showed an unusual perinuclear aggregate of vesicles, heterogeneously positive for lysosomal glycoprotein-B/cathepsin D and rab7, yet negative for the cation-independent mannose 6-phosphate receptor. The aggregate was formed around the microtubule organizing center, and was disrupted by nocodazole treatment. Internalized octadecyl rhodamine B-labeled LDL (R18-LDL) was accumulated in the perinuclear rab7-positive vesicles. In a Percoll density gradient, neither internalized R18-LDL nor internalized horseradish peroxidase was efficiently chased into heavy lysosomal fractions positive for beta-hexosaminidase. LEX1 cells showed differences in the activity and subcellular distribution of lysosomal enzymes. These characteristics of LEX1 cells are consistent with the ideas that the perinuclear vesicle aggregate is an arrested intermediate of direct fusion or divergence between lysosomes and rab7-positive, cation-independent mannose 6-phosphate receptor-negative late endosomes, and that equilibrium between the lysosomes and the late endosomes is shifted towards the late endosomes in LEX1 cells. Such fusion or divergence between the late endosomes and the lysosomes would determine an appropriate equilibrium between them, and might thereby play an important role for proper lysosomal digestive functions. LEX1 mutant cells would be helpful for the dissection of the as yet unrevealed details of the late endocytic membrane dynamics and for the identification of factors involved in the process arrested by the mutation.  (+info)

Endocytic sorting of lipid analogues differing solely in the chemistry of their hydrophobic tails. (8/4632)

To understand the mechanisms for endocytic sorting of lipids, we investigated the trafficking of three lipid-mimetic dialkylindocarbocyanine (DiI) derivatives, DiIC16(3) (1,1'-dihexadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), DiIC12(3) (1,1'- didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate), and FAST DiI (1,1'-dilinoleyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate), in CHO cells by quantitative fluorescence microscopy. All three DiIs have the same head group, but differ in their alkyl tail length or unsaturation; these differences are expected to affect their distribution in membrane domains of varying fluidity or curvature. All three DiIs initially enter sorting endosomes containing endocytosed transferrin. DiIC16(3), with two long 16-carbon saturated tails is then delivered to late endosomes, whereas FAST DiI, with two cis double bonds in each tail, and DiIC12(3), with saturated but shorter (12-carbon) tails, are mainly found in the endocytic recycling compartment. We also find that DiOC16(3) (3,3'- dihexadecyloxacarbocyanine perchlorate) and FAST DiO (3, 3'-dilinoleyloxacarbocyanine perchlorate) behave similarly to their DiI counterparts. Furthermore, whereas a phosphatidylcholine analogue with a BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophore attached at the end of a 5-carbon acyl chain is delivered efficiently to the endocytic recycling compartment, a significant fraction of another derivative with BODIPY attached to a 12-carbon acyl chain entered late endosomes. Our results thus suggest that endocytic organelles can sort membrane components efficiently based on their preference for association with domains of varying characteristics.  (+info)

In the present study, we demonstrated that clathrin and AP-1 are required for the retrograde transport from recycling endosomes to the Golgi. CTxB appeared to reach recycling endosomes in the clathrin- or AP-1-knockdown cells, similar to in control cells, suggesting that clathrin and AP-1 are not essential for the transport of CTxB from the plasma membrane through early endosomes to recycling endosomes. It has been shown that clathrin localizes to the TGN, early endosomes and the plasma membrane (Brodsky, 2012). We showed that CHC also localized to recycling endosomes. CHC colocalized with the recycling endosome proteins, Rab11, Tfn and SMAP2 in COS-1 cells (in which the Golgi, early endosomes and recycling endosomes are spatially distinct) (Lee et al., 2015; Misaki et al., 2007; Uchida et al., 2011). The recycling endosomes that were dispersed from the perinuclear region to the cytoplasm by nocodazole treatment remained positive for CHC. The localization of AP-1 to recycling endosomes (Folsch ...
Regardless of the type of endocytosis, vesicles are fused with an internal membranous compartment known as endosome. Intramecellular compartments formed after phagocytosis and macropinocytosis beccome particular types of endosomes known as phagosome and macropinosome, respectively. Endosomes show an irregular shape, like large bags, although sometimes they form tubular structures. Like the TGN of the Golgi complex , endosomes are stations for receiving and distributing molecules packed in vesicles. Vesicles arrive to endosomes from the plasma membrane and from the TGN of the Golgi complex. From endosomes, vesicles leave toward the plasma membrane or TGN of the Golgi complex, both are pathways for recycling membrane receptors and lipids. However, most of the molecules in the endosomes are transported to lysosomes for degradation. Two ways of endosomal organization have been proposed: a) Cells would contain several types of endosomes. Early endosomes close to the plasma membrane that receive ...
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of these endosomes from the cell cortex and accumulation in the perinuclear space. Depletion of this myosin not only affects endosome positioning, but also induces actin and lipid remodeling consistent with endosome maturation, including accumulation of F-actin and the endosomal lipid PI(3)P. These processes acutely perturb endosome function, as both AKT phosphorylation and RAC-dependent membrane ruffling were markedly reduced by depletion of either APPL1 or MYO6. These results place MYO6 and its binding partners at a central nexus in cellular signaling linking actin dynamics at the cell surface and endosomal signaling in the cell cortex ...
In cell biology, an endosome is a membrane-bounded compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the plasma membrane can follow this pathway all the way to lysosomes for degradation, or they can be recycled back to the plasma membrane. Molecules are also transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization. Endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature. Endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding to the LDL receptor at the cell surface. Upon reaching early endosomes, the LDL ...
P-selectin is not sorted from LDL receptor in late endosomes. P-selectin is transported to the TGN approximately eight to nine times faster than it is delivered to lysosomes in PC12 cells (20-25 min vs. 3-3.8 h), showing that P-selectin molecules entering late endosomes are eight to nine times more likely to recycle to the TGN than to go directly to lysosomes. The ratio of these two transport rates is similar for LDL receptor (t1/2 = 2-2.5 h to the TGN vs. 20 h to lysosomes; Green and Kelly 1992). The simplest explanation for these observations is that both proteins have the same sorting phenotype in late endosomes (Fig. 1A and Fig. B). Therefore, the short half-life of P-selectin is most likely not due to its selective targeting to lysosomes, as has been suggested (Blagoveshchenskaya et al. 1998), but is due to its selective delivery from sorting endosomes to late endosomes. One significant consequence of this sorting event is rapid recycling of P-selectin through the TGN. Rapid turnover of ...
The endocytic pathway is essential for cell homeostasis and numerous small GTPase Rab have been involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis, or adaptative immunity. Here we show that Rab4b is required for early endosome sorting of transferrin receptors (TfR) to the recycling endosomes and we identified the AP1γ subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosomes sorting. We show that internalized transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in absence of Rab4b while it is rapidly recycled back to the plasma membrane. On the contrary, Rab4b overexpression leads to the accumulation of internalized Tf within AP-1 and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except TfR and require AP1γ for their formation. Furthermore, ...
Enveloped viruses fuse with host membranes without affecting cell integrity. Non-enveloped viruses and bacteria penetrate by rupturing endosomal membranes and thus expose complex-type carbohydrates from the endosome lumen to cytosolic proteins. Here we report on the dynamics and initial marker analyses of Galectin-3 (Gal3)-positive membranes triggered by incoming adenovirus species B/C in HeLa cells. Using mCherry-Gal3 reporter constructs, immunolabeling, confocal and electron microscopy, we detected robust signals from Gal3-containing, early endosomal antigen 1-positive membranes 1 h post-infection (pi). Adenoviruses penetrate from non-acidic endosomes with high efficiency, 15 min pi, and largely outnumbered the Gal3-positive membranes, suggesting that Gal3 recruitment to broken membranes is transient, or Gal3-positive membranes are rapidly turned-over. In support of rapid turn-over, Gal3 was found within single-membrane vesicles and degradative autophagosomes. The Gal3 membranes contained ubiquitin
Homotypic fusion between early endosomes requires the phosphatidylinositol 3-phosphate (PI3P)-binding protein, Early Endosomal Autoantigen 1 (EEA1). We have investigated the role of other proteins that interact with EEA1 in the fusion of early endosomes derived from Baby Hamster Kidney (BHK) cells. We confirm a requirement for syntaxin 13, but additionally show that the assay is equally sensitive to reagents specifically targeted against syntaxin 6. Binding of EEA1 to immobilised GST-syntaxin 6 and 13 was directly compared; only syntaxin 6 formed a stable complex with EEA1. Early endosome fusion requires the release of intravesicular calcium, and calmodulin plays a vital role in the fusion pathway, as judged by sensitivity to antagonists. We demonstrate that both EEA1 and syntaxin 13 interact with calmodulin. In the case of EEA1, binding to calmodulin requires an IQ domain, which is adjacent to a C-terminal FYVE domain that specifically binds to PI3P. We have assessed the influence of protein binding
Genetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLC beta/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of ...
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes which are proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The HOPS complex is proposed to be recruited to Rab7 on the late endosomal membrane and to regulate late endocytic, phagocytic and autophagic traffic towards lysosomes. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:11382755, PubMed:23351085, PubMed:24554770, PubMed:25266290, PubMed:25783203). Required for recruitment of VPS33A to the HOPS complex (PubMed:23901104). Required for fusion of endosomes and autophagosomes with lysosomes; the
Influenza viruses enter the cell inside an endosome. During the endosomal journey, acidification triggers a conformational change of the virus spike protein hemagglutinin (HA) that results in escape of the viral genome from the endosome into the cytoplasm. It is still unclear how the interplay between acidification and HA conformation changes affects the kinetics of the viral endosomal escape. We develop here a stochastic model to estimate the change of conformation of HAs inside the endosome nanodomain. Using a Markov process, we model the arrival of protons to HA binding sites and compute the kinetics of their accumulation. We compute the Mean First Passage Time (MFPT) of the number of HA bound sites to a threshold, which is used to estimate the HA activation rate for a given pH (i.e. proton concentration). The present analysis reveals that HA proton binding sites possess a high chemical barrier, ensuring a stability of the spike protein at sub -acidic pH. We predict that activating more than ...
Mutations in CHMP2B, encoding a protein in the endosomal sorting complexes required for transport (ESCRT) machinery, causes frontotemporal dementia linked to chromosome 3 (FTD3). FTD, the second most common form of pre-senile dementia, can also be caused by genetic mutations in other genes, including TANK-binding kinase 1 (TBK1). How FTD-causing disease genes interact is largely unknown. We found that partial loss function of Ik2, the fly homologue of TBK1 also known as I-kappaB kinase epsilon (IKKepsilon), enhanced the toxicity of mutant CHMP2B in the fly eye and that Ik2 overexpression suppressed the effect of mutant CHMP2B in neurons. Partial loss of function of Spn-F, a downstream phosphorylation target of Ik2, greatly enhanced the mutant CHMP2B phenotype. An interactome analysis to understand cellular processes regulated by Spn-F identified a network of interacting proteins including Spn-F, Ik2, dynein light chain, and Hook, an adaptor protein in early endosome transport. Partial loss of function
CD63 (Late Endosomes Marker) Antibody - With BSA and Azide, Purified Mouse Monoclonal Antibody validated in WB, IHC, IF, FC, IP, E (AH10281-20), Abgent
Probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, may act as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation. May be involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking. Alternatively, may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. May indirectly play a role in neurite outgrowth.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
Membranes are vital barriers by which cells control the flux of molecules and energy between their exterior and interior and also between their various intracellular compartments. While numerous transport systems exist for ions and small molecules, the cytosolic uptake of larger biological molecules and in particular antibody-targeted drugs, is a big challenge. Inducing leakage of the plasma membrane is unfavorable since the target cell specificity mediated by the antibody would likely be lost in this case. After binding and internalization, the antibody drug conjugates reach the endosomes. Thus, enforcing the endosomal escape of anti-tumor toxins without affecting the integrity of other cellular membranes is of paramount importance. Different strategies have been developed in the last decades to overcome endosomal accumulation and subsequent lysosomal degradation of targeted protein-based drugs. In this review we summarize the various efforts made to establish efficient techniques to disrupt the
In this study, we uncover a novel molecular player important for axon branching and compartmentalization. We demonstrate that Clstn-1 is critical for growth and branching of peripheral sensory axons and differentially affects the behavior of separate axons from one neuron. Furthermore, our data indicate that Clstn-1 acts in part through a trafficking role and controls the transport of endosomal carriers. Our ability to image live endosome dynamics as vertebrate neurons develop complex axon arborizations in vivo has revealed new insight into Clstn-1 function and into differential endosome dynamics in specific axon compartments. Our results suggest that regulated trafficking of early endosomes from the cell body to specific axon locations is crucial for neuronal compartmentalization and axon branching.. Precise control over axon branching is essential for neuronal circuit formation. Many factors have been shown to influence axon branching, including extracellular cues, intracellular signaling ...
A diverse assortment of peptides mediates cellCcell communication. the anticipated enrichment in the endosomal markers Rab-5 and early endosome antigen 1 (Fig. S3). To make sure that the endosomal fractions had been free from any significant quantity of plasma membrane, we subjected examples to European blot evaluation with antibodies against the Na+/K+ ATPase (Fig. S3). We were not able to detect Na-K ATPase in the endosomal portion, estimating a recognition limit of 0.01% contamination predicated on the Na-K ATPase staining strength in the plasma membrane fraction. On the other hand, the approximated endosomal content material of IDE was 0.22% of the full total IDE put on the sucrose gradient. These data show that IDE within the endosomal portion isnt an artifact because of contaminants of endosomes with additional cellular components. Open up in another windows Fig. 5. Endosomal IDE content material of COS-1 cells. (display magnified views from the areas indicated by small rectangles to ...
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When released from the 20°C block, VSVG emigrated away from membranes positive for conventional Golgi to closely apposed structures that were positive for AP-1B and Exo70. Intriguingly, Exo70 also strongly localized to Tfn- and TfnR-positive recycling endosomes. Thus, it seems possible that AP-1B-dependent cargo may at least partially enter recycling endosomes before continuing to the plasma membrane after exit from the Golgi. Our data are thus in agreement with previous observations showing that Rab11 (a recycling endosome-associated GTPase) may play a role in biosynthetic traffic, at least in nonpolarized cells (Chen et al., 1998). Moreover, both the TGN and recycling endosomes are complex sorting compartments (Mellman and Warren, 2000). In the case of epithelial cells, it is also interesting to note that polarized targeting of newly synthesized and recycling glycoproteins makes use of similar or identical sorting determinants in the TGN and in the endocytic pathway (Matter et al., 1993; ...
MAJOR ISSUES The reviewers were not fully convinced by the endosome acidification results. Both wanted a more thorough characterization of endosome distribution and transferrin colocalization in the transferrin experiments and felt that more detail - in particular, relative to the calculation of the n values - were needed to judge the robustness of the pH experiments. 1. RE: N values and figures chosen: The authors must specify how many cells, how many different cultures from how many different animals were used for the determinations of transferrin (Fig 3) and for the assays of endosome acidification (Fig 4). Both reviewers felt that the number of endosomes tested was relatively small. These n values should be increased. Response: To address this question, we developed a method using a high-throughput confocal fluorescence imaging system, the Opera Phenix High Content Screening System, which allowed us to image and analyze thousands of cells and endosomes. Based on use of this new method and ...
Supplementary MaterialsS1 Fig: EHBP-1 deficient N-terminal C2-like or central CH domain didnt save the intestinal vacuole (bigger endosome) phenotype. indicate EHBP-1(NT-C2)-GFP and EHBP-1(CH)-GFP tagged puncta in the intestinal cells. Arrows reveal EHBP-1(CH)-GFP tagged intestinal vacuoles. (E-F) Intestinal manifestation of CH-CC fragment (EHBP-1(NT-C2)) disrupted recycling cargo hTAC-GFP tubular endosomal localization. (G-G) hTAC-GFP misplaced tubular endosomal localization and gathered on punctate constructions upon the knockdown of PPK-1. (H-I) Manifestation of CH-CC fragment triggered intracellular accumulation of recycling cargo hTAC-GFP about enlarged vacuoles and endosomes. Arrows reveal hTAC-GFP tagged intestinal vacuoles. Size bars stand for 10 m.(TIF) pgen.1006093.s002.tif (2.0M) GUID:?266611FC-D3A5-437B-A587-32B44A93EE3D S3 Fig: Association of EHBP-1 fragments with RAB-10 and ARF-6 tagged endosomes. Colocalization pictures are from confocal picture stacks obtained in intestinal ...
Seroussi, E., Kedra, D., Kost-Alimova, M., Sandberg-Nordqvist, A., Fransson, I., Jacobs, J., ... Dumanski, J. (1999). TOM1 Genes Map to Human Chromosome 22q13.1 and Mouse Chromosome 8C1 and Encode Proteins Similar to the Endosomal Proteins HGS and STAM. Genomics, 57, 380 - 388 ...
J Immunol. 2008 Jun 15;180(12):8192-203. Platelet-activating factor-mediated endosome formation causes membrane translocation of p67phox and p40phox that requires recruitment and activation of p38 MAPK, Rab5a, and phosphatidylinositol 3-kinase in human neutrophils. McLaughlin NJ, Banerjee A, Khan SY, Lieber JL, Kelher MR, Gamboni-Robertson F, Sheppard FR, Moore EE, Mierau GW, Elzi DJ, Silliman CC ...
The total amount of p-EGFR in endosomes decays with the same kinetics asthe number of endosomes with p-EGFR.Time course of total integral p-EGFR intensity in en
Predicted to have phosphatidylinositol-3-phosphate binding activity. Involved in erythrocyte differentiation; heme biosynthetic process; and hemoglobin biosynthetic process. Predicted to localize to early endosome membrane and retromer complex. Is expressed in digestive system; hematopoietic system; and vascular endothelium. Human ortholog(s) of this gene implicated in syndromic microphthalmia 8. Orthologous to human SNX3 (sorting nexin 3 ...
Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN ...
The collection of specimens illustrated in this section demonstrates the effectiveness of the Nikon YFP HYQ filter combination with a series of cell lines containing a chimeric EYFP plasmid vector that expresses a fluorescent fusion protein targeted at the cellular endosomal network.
This elegant study identifies Arc as a presenilin-1 (PS1) interacting protein that links synaptic activity with γ-secretase processing of APP in neurons. Detailed analysis of subcellular localization of APP, PS1, and Arc by immunofluorescence and immunoelectron microscopy methods suggest a mechanism whereby Arc facilitates association of PS1 with endosomes that contain internalized APP. Thus, it appears that the subset of APP that contributes to activity-dependent Aβ production encounters PS1 in endocytic organelles in dendrites of excitatory neurons.. Arc is known to associate with endophilin-2/3 and dynamin on endosomes, and mediate AMPA receptor (AMPAR) endocytosis. Whereas the last is markedly reduced in Arc knockout neurons, this does not appear to be the case with PS1 or APP. Whether this indicates Arc regulation of PS1/APP colocalization in tubulovesicular endosomes is distinct from its function in regulating the endocytic machinery responsible for AMPAR endocytosis remains to be ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene is a member of the Sec-1 domain family, and it encodes a protein similar to the yeast class C Vps33 protein. The mammalian class C VPS proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. [provided by RefSeq, Jul 2008 ...
Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is a prominent substrate for activated tyrosine kinase receptors that has been proposed to play a role in endosomal membrane trafficking. The protein contains a FYVE domain, which specifically binds to the lipid phosphatidylinositol (PI) 3-phosphate (PI 3-P). We show that this interaction is required both for correct localization of the protein to endosomes that only partially coincides with early endosomal autoantigen 1 and for efficient tyrosine phosphorylation of the protein in response to epidermal growth factor stimulation. Treatment with wortmannin reveals that Hrs phosphorylation also requires PI 3-kinase activity, which is necessary to generate the PI 3-P required for localization. We have used both hypertonic media and expression of a dominant-negative form of dynamin (K44A) to inhibit endocytosis; under which conditions, receptor stimulation fails to elicit phosphorylation of Hrs. Our results provide a clear example of the
Immune responses are initiated when molecules of microbial origin are sensed by the Toll-like receptors (TLRs). We now report the identification of essential molecular components for the trafficking of the lipopolysaccharide (LPS) receptor complex. LPS was endocytosed by a receptor-mediated mechanism dependent on dynamin and clathrin and colocalized with TLR4 on early/sorting endosomes. TLR4 was ubiquitinated and associated with the ubiquitin-binding endosomal sorting protein hepatocyte growth factor-regulated tyrosine kinase substrate, Hrs. Inhibition of endocytosis and endosomal sorting increased LPS signaling. Finally, the LPS receptor complex was sorted to late endosomes/lysosomes for degradation and loading of associated antigens onto HLA class II molecules for presentation to CD4+ T cells. Our results show that endosomal trafficking of the LPS receptor complex is essential for signal termination and LPS-associated antigen presentation, thus controlling both innate and adaptive immunity through
Phosphatidylinositol 3-phosphate [PtdIns(3)P] regulates endocytic trafficking and the sorting of receptors through early endosomes, including the rapid recycling of transferrin (Tfn). However, the phosphoinositide phosphatase that selectively opposes this function is unknown. The myotubularins are a family of eight catalytically active and six inactive enzymes that hydrolyse PtdIns(3)P to form PtdIns. However, the role each myotubularin family member plays in regulating endosomal PtdIns(3)P and thereby endocytic trafficking is not well established. Here, we identify the myotubularin family member MTMR4, which localizes to early endosomes and also to Rab11- and Sec15-positive recycling endosomes. In cells with MTMR4 knockdown, or following expression of the catalytically inactive MTMR4, MTMR4(C407A), the number of PtdIns(3)P-decorated endosomes significantly increased. MTMR4 overexpression delayed the exit of Tfn from early endosomes and its recycling to the plasma membrane. By contrast, expression of
Endosomal internalisation and subsequent lysosomal degradation of membrane proteins is important for regulation of multiple cellular processes, among these the termination of receptor signalling and degradation of misfolded membrane proteins. ESCRT (Endosomal sorting complex required for transport) proteins are vital for the sorting of ubiquitinated membrane proteins into multivesicular bodies for subsequent degradation in the lysosome. In this study we generated two stable cell lines expressing the EGFP tagged ESCRT proteins Hrs and hVps22. Our goal was to utilise these cell lines for investigations into ESCRT protein dynamics, the relative order of ESCRT protein recruitment to the endosomes, and the endosomal localisation of ESCRT proteins. However, though the EGFP-Hrs cell line seemed to express a functional Hrs protein, the EGFP-hVps22 protein was completely cytosolic and could not be visualised on endosomes. hVps4, and its mouse homologue Skd1 is an AAA-type ATPase shown to be necessary for ...
It is well established that dynamin is involved in clathrin-dependent endocytosis, but relatively little is known about possible intracellular functions of this GTPase. Using confocal imaging, we found that endogenous dynamin was associated with the plasma membrane, the trans-Golgi network, and a perinuclear cluster of cation-independent mannose 6-phosphate receptor (CI-MPR)-containing structures. By electron microscopy (EM), it was shown that these structures were late endosomes and that the endogenous dynamin was preferentially localized to tubulo-vesicular appendices on these late endosomes. Upon induction of the dominant-negative dynK44A mutant, confocal microscopy demonstrated a redistribution of the CI-MPR in mutant-expressing cells. Quantitative EM analysis of the ratio of CI-MPR to lysosome-associated membrane protein-1 in endosome profiles revealed a higher colocalization of the two markers in dynK44A-expressing cells than in control cells. Western blot analysis showed that ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Due to its nitrogen structure, Chloroquine can enter cells and endosomal membranes involved in transport within the cell Mar 17, 2020 · Specifically, the CDC research was completed in primate cells using chloroquines well known function of elevating endosomal pH. Cited by: 16 Publish Year: 2017 Author: Md. Co-incubation of cells with distinctly labeled K8- and R8-modified nanoparticles confirmed chloroquine endosomal release a common uptake pathway and different rates of endosomal escape particularly at longer time intervals. 2007 ) Chloroquine is a weak base which can partition into acidic vesicles such as endosomes and lysosomes, resulting in inhibition of endosomal acidification and lysosomal enzyme activity. Teva-Chloroquine may be available in the countries listed below. 2002). A positive control sample was exposed to chloroquine prior to imaging Chloroquine, a 9-aminoquinoline that was identified in 1934, is a weak base that increases the pH of acidic vesi-cles. Rab27b is one of several ...
We identified p18 as a potential component of lipid rafts. The predominant distribution of p18 to DRMs suggested its potential localization to lipid rafts. However, it is currently accepted that DRMs do not necessarily correspond to lipid rafts and that the DRM separation method is insufficient for the identification of lipid raft‐associated proteins (Lichtenberg et al, 2005; Hancock, 2006). Thus, to verify the raft localization of p18, we examined intracellular distribution of p18 and its mutants. The cell staining analyses showed that p18 could be colocalized with GM1 ganglioside, a marker of lipid rafts (Harder et al, 1998), and that the N‐terminal potential myristoylation and palmitoylation sites, which are known to function as lipid raft localization signals, were required for the late endosome localization of p18. These observations strongly supported the presence of p18 in lipid rafts of late endosomes (Balbis et al, 2007). It is of interest that the N‐terminal only 20 residues of ...
Looking for online definition of recycling endosome in the Medical Dictionary? recycling endosome explanation free. What is recycling endosome? Meaning of recycling endosome medical term. What does recycling endosome mean?
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TY - JOUR. T1 - Brefeldin A rapidly disrupts plasma membrane polarity by blocking polar sorting in common endosomes of MDCK cells. AU - Wang, E.. AU - Pennington, J. G.. AU - Goldenring, J. R.. AU - Hunziker, W.. AU - Dunn, Kenneth. PY - 2001. Y1 - 2001. N2 - Recent studies showing thorough intermixing of apical and basolateral endosomes have demonstrated that endocytic sorting is critical to maintaining the plasma membrane polarity of epithelial cells. Our studies of living, polarized cells show that disrupting endocytosis with brefeldin-A rapidly destroys the polarity of transferrin receptors in MDCK cells while having no effect on tight junctions. Brefeldin-A treatment induces tubulation of endosomes, but the sequential compartments and transport steps of the transcytotic pathway remain intact. Transferrin is sorted from LDL, but is then missorted from common endosomes to the apical recycling endosome, as identified by its nearly neutral pH, and association with GFP chimeras of Rabs 11a and ...
In endocytosis small GTPases Rab5 and Rab7 act like molecular switches and regulate vesicular transport and membrane trafficking. Rab5 represents a marker of early endosomes which is essential for homotypic and heterotypic fusion as well for endosome motility while Rab7 represents a marker of late endosomes. Conversion from Rab5 to Rab7 is important for the course of an endolysosomal path. Purpose of this thesis was to investigate correlation between endosome maturation and proplatelet formation. We used Western blot analysis to examine the level of expression of early (Rab5), late (Rab7) and recycling (Rab11) endosomes in different maturation stages of mouse megakaryocytes and platelets. By immunofluorescence and confocal microscopy, we analyzed the localization of early (Rab5, EEA1) and late (Rab7, LAMP1) endosomes considering the maturation stage of megakaryocytes. In addition, we treated megakaryocytes with inhibitors that cause rapid alkalinization of acidic organelles and block conversion ...
Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease ...
The small GTP-binding protein rab5 was previously localized on early endosomes and on the cytoplasmic face of the plasma membrane. Using a cell-free assay, we have now tested whether rab5 is involved in controlling an early endocytic fusion event. Fusion could be inhibited by cytosol containing the …
CHMP2B Full-Length MS Protein Standard (NP_054762), Labeled with [U- 13C6, 15N4]-L-Arginine and [U- 13C6, 15N2]-L-Lysine, was produced in human 293 cells (HEK293) with fully chemically defined cell culture medium to obtain incorporation efficiency at Creative-Proteomics. This gene encodes a component of the heteromeric ESCRT-III complex (Endosomal Sorting Complex Required for Transport III) that functions in the recycling or degradation of cell surface receptors. ESCRT-III functions in the concentration and invagination of ubiquitinated endosomal cargos into intralumenal vesicles. The protein encoded by this gene is found as a monomer in the cytosol or as an oligomer in ESCRT-III complexes on endosomal membranes. It is expressed in neurons of all major regions of the brain. Mutations in this gene result in one form of familial frontotemporal lobar degeneration.
The retromer is a phylogenetically conserved multisubunit complex that mediates retrograde transport of transmembrane cargo from endosomes to the TGN (Seaman, 2005; Bonifacino and Rojas, 2006; Bonifacino and Hurley, 2008). The best-characterized cargo for the mammalian retromer is the cation-independent mannose 6-phosphate receptor (MPR [CI-MPR]), one of two intracellular sorting receptors that participates in the delivery of acid hydrolases to lysosomes (Kornfeld, 1992). The CI-MPR binds newly synthesized acid hydrolases at the TGN and carries them within clathrin-coated vesicles to endosomes, where the hydrolases are released for eventual transport to lysosomes. The retromer functions to retrieve the unoccupied receptors to the TGN, where they engage in further cycles of acid hydrolase sorting. Depletion of retromer subunits by RNAi prevents this retrieval, leading to rerouting of the receptors to lysosomes and consequent leakage of newly synthesized acid hydrolases into the extracellular ...
Supplementary MaterialsFigure S1: Internalization assay. endosomes associated with dynamic actin assemblies. 3T6 cells stably expressing EGFP-fused -actin (green) were infected with Alexa Fluor 546-labeled MPyV (reddish) (MOI of 102 to 103 computer virus particles per cell) at 37C and scanned with T?=?4 s. Selected frames of cell at 45 min p.i. with corresponding transmission light images illustrate short-distance movement of virus-carrying endosomes associated with dynamic assemblies of EGFP-actin (observe Movie S3). White colored arrowheads point to MPyV virions. Arrows point to endosome-associated actin assemblies. Black arrowheads show MPyV-containing endosomes. Bars, 5 m. Cells were examined using a Leica TCS SP2 AOBS confocal microscope.(TIF) pone.0096922.s002.tif (4.6M) GUID:?75128633-6C0E-4733-829A-F64BA5BC7B02 Number S3: Intracellular distribution of fluorescently tagged transferrin during expression of Rab11 GTPase mutants. 3T6 cells expressing EGFP-fused wt, DN or CA version of Rab11 ...
Little is known about the molecular players that regulate changes in the endocytic pathway during immune activation. Here we investigate the role of Rab20 in the endocytic pathway during activation of macrophages. Rab20 is associated with endocytic structures, but the function of this Rab GTPase in the endocytic pathway remains poorly characterized. We find that in macrophages, Rab20 expression and endosomal association significantly increase after interferon-γ (IFN-γ) treatment. Moreover, IFN-γ and Rab20 expression induce a dramatic enlargement of endosomes. These enlarged endosomes are the result of homotypic fusion promoted by Rab20 expression. The expression of Rab20 or the dominant-negative mutant Rab20T19N does not affect transferrin or dextran 70 kDa uptake. However, knockdown of Rab20 accelerates epidermal growth factor (EGF) trafficking to LAMP-2-positive compartments and EGF receptor degradation. Thus this work defines a function for Rab20 in the endocytic pathway during immune ...
Anterograde transport of late endosomes or lysosomes (LE/Lys) is crucial for proper axon growth. However, the role of energetic nutrients has been poorly explored. Malonyl-CoA is a precursor of fatty acids, and its intracellular levels highly fluctuate depending on glucose availability or the energy sensor AMP-activated protein kinase (AMPK). We demonstrate in HeLa cells that carnitine palmitoyltransferase 1C (CPT1C) senses malonyl-CoA and enhances LE/Lys anterograde transport by interacting with the endoplasmic reticulum protein protrudin and facilitating the transfer of Kinesin-1 from protrudin to LE/Lys. In cultured mouse cortical neurons, glucose deprivation, pharmacological activation of AMPK or inhibition of malonyl-CoA synthesis decreases LE/Lys abundance at the axon terminal, and shortens axon length in a CPT1C-dependent manner. These results identify CPT1C as a new regulator of anterograde LE/Lys transport in response to malonyl-CoA changes, and give insight into how axon growth is ...
We data-analyzed and constructed the high-expression CAMK1 phosphoinositide signal-mediated protein sorting and transport network in human hepatocellular carcinoma (HCC) compared with low-expression (fold change ≥ 2) no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, using integration of gene regulatory network inference method with gene ontology (GO). Our result showed that CAMK1 transport subnetwork upstream KCNQ3, LCN2, NKX2_5, NUP62, SORT1, STX1A activated CAMK1, and downstream CAMK1-activated AFP, ENAH, KPNA2, SLC4A3; CAMK1 signal subnetwork upstream BRCA1, DKK1, GPSM2, LEF1, NR5A1, NUP62, SORT1, SSTR5, TBL3 activated CAMK1, and downstream CAMK1-activated MAP2K6, SFRP4, SSTR5, TSHB, UBE2C in HCC. We proposed that CAMK1 activated network enhanced endosome to lysosome transport, endosome transport via multivesicular body sorting pathway, Golgi to endosome transport, intracellular protein transmembrane transport, intracellular protein transport, ion transport, mRNA ...
The mechanisms by which altered processing, distribution and secretion of proteolytic enzymes occur, facilitating degradation of the extracellular matrix in invasive and metastatic cells, are not fully understood. Studies on the MCF-10 A breast epithelial cell line and its premalignant, c-Ha-ras-transfected MCF-10AneoT counterpart have shown that the ras-transfected cell line has a more alkaline pH. The objective of this study was to determine which organelles of the endosome-lysosome route were alkalinized and shifted to the cell periphery after ras-transfection. Antibodies to the hapten 2,4-dinitrophenyl (DNP), required for pH studies, were raised in rabbits and chickens using DNP-ovalbumin (DNP-OVA) as immunogen. Cationised DNP-OVA (DNP-catOVA) was also inoculated to increase antibody titres. Anti-hapten and carrier antibody titres were assessed. In rabbits, cationisation seems useful to increase anti-DNP titres if a non-self carrier protein (OVA) is used. In chickens, cationisation of ...
Jacob, A., and Prekeris, R. (2015) Regulation of MMP targeting to invadopodia during cancer metastasis. Frontiers in Cell and Developmental Biology. In Press.. Mangan, A., and Prekeris, R. (2015) 3D-Time-Lapse analysis of Rab11/FIP5 complex: spatiotemporal dynamics during apical lumen formation. Methods in Molecular Biology. In Press.. Li, D., Kuehn, E.W., and Prekeris, R. (2014) Kinesin-2 mediates apical endosome transport during epithelial lumen formation. Cellular Logistics. In Press.. Li, D., Mangan, A., Ciccini, L., Margolis, B., and Prekeris, R. (2014) FIP5 phosphorylation during mitosis regulates apical trafficking and luminogenesis. EMBO reports. 15(4):428-437.. Jacob, A., Jing, J., Lee, J., Schedin, P., Peden, A.A., Junutula, J.R. and Prekeris, R. (2013) Rab40b regulates MMP2 and MMP9 trafficking during invadopodia formation and breast cancer cell invasion. Journal of Cell Science. 126:4647-4658.. Schiel, J., Childs, C., and Prekeris, R. (2013) Endocytic transport and cytokinesis: from ...
This is calculation with bound lipids. Acyl chains of two lipids were modelled. Calculated hydrocarbon boundary of the lipid bilayer corresponds to the carbonyl groups of the bound lipid. Depending on conformations of bound lipids, the protein can penetrate deeper by ~2 A. Results for the dimer without bound lipids are exactly the same as for lipid-free EEA1 monomer (1hyi). Transfer energy was calculated without contribution from the bound lipid ...
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene comprise the most common cause of familial Parkinsons disease (PD), and variants increase the risk for sporadic PD. LRRK2 displays kinase and GTPase activity, and altered catalytic activity correlates with neurotoxicity, making LRRK2 a promising therapeutic target. Despite the importance of LRRK2 for disease pathogenesis, its normal cellular function, and the mechanism(s) by which pathogenic mutations cause neurodegeneration remain unclear. LRRK2 seems to regulate a variety of intracellular vesicular trafficking events to and from the late endosome in a manner dependent on various Rab proteins. At least some of those events are further regulated by LRRK2 in a manner dependent on two-pore channels (TPCs). TPCs are ionic channels localized to distinct endosomal structures and can cause localized calcium release from those acidic stores, with downstream effects on vesicular trafficking. Here, we review current knowledge about the link ...
If you have a question about this talk, please contact Mihoko Tame.. Abstract not available. This talk is part of the Developmental Biology Seminar Series series.. ...
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In this work, we have shown that RME‐8 and SNX‐1 are required to rescue MIG‐14 from degradation after its endocytosis. Our results showing the aberrant sorting and degradation of MIG‐14 in snx‐1 and rme‐8 mutants are quite similar to those earlier shown for CI‐M6PR after co‐depletion of Snx1 and Snx2, or single depletion of other retromer components, in mammalian cells (Rojas et al, 2007). Our results are also reminiscent of the aberrant sorting and degradation of the EGF‐R after siRNA‐mediated depletion of RME‐8 in mammalian cells (Girard and McPherson, 2008). In fact, this similarity in phenotype may indicate that a fraction of EGF‐Rs recycle through the retrograde endosome to Golgi pathway.. However, CI‐M6PR steady‐state levels were not reported to be reduced after siRNA‐mediated depletion of RME‐8 (Girard et al, 2005). Rather, CI‐M6PR was reported to aberrantly accumulate in or near the Golgi (Girard et al, 2005). We do not yet understand this apparent ...
Protein present in Fab1, YOTB, Vac1, and EEA1. The FYVE zinc finger is named after four proteins where it was first found: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn2+ ions. The FYVE finger has eight potential zinc coordinating cysteine positions. The FYVE finger is structurally related to the PHD finger and the RING finger. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. The FYVE finger functions in the membrane recruitment of cytosolic proteins by binding to phosphatidylinositol 3-phosphate (PI3P), which is prominent on endosomes. The R+HHC+XCG motif is critical for PI3P binding. ...
Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10066790, PubMed:10436028). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. AP-4 is involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos, but may also recognize other types of sorting signal (Probable). ...
Alix [ALG-2 (apoptosis-linked gene 2)-interacting protein X] is a ubiquitinous adaptor protein first described for its capacity to bind to the calcium-binding protein, ALG-2. Alix regulates neuronal death in ways involving interactions with ALG-2 and with proteins of the ESCRT (endosomal sorting complex required for transport). Even though all Alix interactors characterized to date are involved in endosomal trafficking, the genuine function of the protein in this process remains unclear. We have demonstrated recently that Alix and ALG-2 form in the presence of calcium, a complex with apical caspases and with the endocytosed death receptor TNFR1 (tumour necrosis factor α receptor 1), thus suggesting a molecular coupling between endosomes and the cell death machinery.. ...
Endosomal-lysosomal pH defects are an emerging theme in mechanisms underlying a number of neurodegenerative diseases. To date, results from experiments in vivo and in vitro have revealed the importance of proper vesicular pH balance and optimal acidification in transporting and degrading cargo via the endocytic pathway [48, 49]. For instance, Lee et al. reported that, in presenilin1 (PSEN1)-deleted blastocysts, defective lysosome acidification was observed with a substaintially elevated lysosomal PH of 5.4 and PSEN1 is essential for the transport of mature V0a1 subunites of V-ATP to lysosomes for their acidification and proteolysis [50]. Specifically, dysregulation of acidification and intracellular pH perturbation could influence the activity of enzymes in endomembrane compartments, resulting in impaired clearance of protein aggregates downstream of elevated endomembrane system pH, or conversely, due to decreased cytoplasmic pH. Regarding the latter, asparaginyl endopeptidase (AEP) is a typical ...
Rab5兔多克隆抗体(ab31261)可与果蝇样本反应并经WB, IHC, ICC/IF实验严格验证,被12篇文献引用并得到6个独立的用户反馈。所有产品均提供质保服务,中国75%以上现货。
Molecular motors generate the force needed for long-distance transport of cargos and organelles in the cell. How motor proteins attach to a diverse array of cargos and navigate to the correct location in the cell with enough fidelity to maintain organelle integrity is only starting to be understood. Studying the properties of individual motors, and their fine-tuning by regulatory molecules, is one area of active investigation in vitro. However, the organization of the cell, and the variability of the environment within a single cell, cannot be fully reconstituted in vitro. We investigated the effects of the crowded intracellular environment on early endosomal trafficking. Live-cell imaging of an endosomal cargo (endocytosed epidermal growth factor-conjugated quantum dots) combined with high-resolution tracking was used to analyze the heterogeneous motion of individual endosomes. The motile population of endosomes moved towards the perinuclear region in directed bursts of microtubule-based, dynein
Distinct effects of endosomal escape and inhibition of endosomal trafficking on gene delivery via electrotransfection.s profile, publications, research topics, and co-authors
Location, location, location. Among those who suggest this real estate mantra deserves higher priority in Alzheimer disease drug design are scientists in Germany who have created a membrane-tethered version of a β-secretase inhibitor. In todays issue of Science, the researchers report that this modified inhibitor reaches endosomes, the subcellular compartments containing active β-secretase, and greatly outperforms free inhibitor at blocking the enzymes activity in cultured cells and in fruit fly and mouse models. While these findings represent a proof of principle for the membrane-anchoring approach, the new strategy faces tough hurdles en route to practical drug therapy.. BACE1, the transmembrane protein that confers β-secretase activity, has become a prime AD drug target in large part because it plays a key role in generating Aβ peptide, whose accumulation in plaques represents a hallmark feature of AD. Partnering with a complex of proteins known as γ-secretase, BACE1 catalyzes the ...
The association of the Vps35-Vps29-Vps26 complex to the cytosolic domains of cargo molecules endosomal membranes initiates the activation of retrograde trafficking and cargo capture.[16] The nucleation complex was formed through the interaction of VPS complex with GTP-activated Rab7[17] with clathrin, clathrin-adaptors and various binding proteins.[18]. The SNX-BAR dimer enters the nucleation complex via direct binding or lateral movement on endosomal surface. The increased level of Retromer SNX-BARs causes a conformational switch to a curvature-inducing mode which initiates membrane tubule formation.[19][20] Once the cargo carriers are matured, the carrier scission is then catalyzed by dynamin-II or EHD1,[21] together with the mechanical forces generated by actin polymerization and motor activity.. The cargo carrier is transported to the TGN by motor proteins such as dynein. Tethering of the cargo carrier to the recipient compartment will lead to the uncoating of the carrier which is driven by ...
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All in all, the results of the Gal-3 studies in COS cells paint a largely coherent picture of intracellular transport (Figure 3). The first contact between Gal-3 and the glycoproteins it sorts presumably takes place in a still unidentified post-Golgi compartment. By manipulating the pH, it was possible for the first time to localise YFP-labeled Gal-3 in endosomal compartments which are probably EEs (early endosomes) or REs (recycling endosomes) and which are discussed as the possible location of post-Golgi sorting. The vesicles formed by budding could then be transported via microtubules and then switch to actin microfilaments (Figure 2) in the vicinity of the membrane. After fusion of the vesicles with the membrane, the apical glycoproteins sorted by Gal-3 have reached their destination and are distributed together with Gal-3 in the membrane. However, a different mechanism seems to be responsible for transporting Gal-3 into the inside the cell interior. Whereas Gal-3 is important for the apical ...
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There are three different types of endosomes: early endosomes, late endosomes, and recycling endosomes. They are distinguished ... Early endosomes then mature into late endosomes before fusing with lysosomes. Early endosomes mature in several ways to form ... which is only found in late endosomes, endolysosomes or lysosomes. When the endosome has matured into a late endosome/MVB and ... returns from the early endosome to the cell surface, both directly and via recycling endosomes. Transport from late endosomes ...
This gene encodes a protein involved in endosomal sorting of cell surface receptors via a multivesicular body/late endosome ... Raiborg C, Rusten TE, Stenmark H (2004). "Protein sorting into multivesicular endosomes". Curr. Opin. Cell Biol. 15 (4): 446-55 ... "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. 276 ( ... "TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes". J. Biol. Chem. 276 ( ...
... had no effect on the transport of endosomes devoid of the rabies virus. (Rabies resides in nerve endosomes). But ... endosomes carrying the virus were either completely immobilized, or were only able to move short distances at slower-than- ...
Seet LF, Liu N, Hanson BJ, Hong W (2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. 279 (6): 4670-4679. doi:10.1074/ ... 2005). "Overexpression of Rab22a hampers the transport between endosomes and the Golgi apparatus". Exp. Cell Res. 304 (2): 339- ... 2006). "Rab22a regulates the sorting of transferrin to recycling endosomes". Mol. Cell. Biol. 26 (7): 2595-2614. doi:10.1128/ ...
Seet LF, Liu N, Hanson BJ, Hong W (2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. 279 (6): 4670-9. doi:10.1074/jbc ... Seet LF, Hong W (2005). "Endofin recruits clathrin to early endosomes via TOM1". J. Cell Sci. 118 (Pt 3): 575-87. doi:10.1242/ ... Seet, Li-Fong; Liu Ningsheng; Hanson Brendon J; Hong Wanjin (Feb 2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. ... "Tollip and Tom1 form a complex and recruit ubiquitin-conjugated proteins onto early endosomes". J Biol Chem. 279 (23): 24435-43 ...
Seet LF, Liu N, Hanson BJ, Hong W (2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. 279 (6): 4670-9. doi:10.1074/jbc ...
Seet LF, Liu N, Hanson BJ, Hong W (February 2004). "Endofin recruits TOM1 to endosomes". The Journal of Biological Chemistry. ... Seet LF, Liu N, Hanson BJ, Hong W (February 2004). "Endofin recruits TOM1 to endosomes". The Journal of Biological Chemistry. ...
In turn, parts of the membranes of some endosomes are subsequently internalized as smaller vesicles. Such endosomes are called ... The multivesicular body (MVB) is an endosome with intraluminal vesicles (ILVs) that bud inward into the endosomal lumen. If the ... Exosome formation starts with the invagination of the multi-vesicular bodies (MVBs) or late endosomes to generate intraluminal ... The internalized exosomes are targeted to the endosomes which release their content in the recipient cell. Exosomes contain ...
... localizes to early endosomes where it is involved in the recruitment of RAB7A and the maturation of these compartments to ... It drives the maturation of endosomes by transporting vacuolar (H+)-ATPases (V-ATPases) from trans-Golgi network to endocytic ... "Entrez Gene: RAB5A RAB5A, member RAS oncogene family". Huotari J, Helenius A (Aug 2011). "Endosome maturation". The EMBO ... is complexed with hVPS45 and recruited to endosomes through a FYVE finger domain". The Journal of Cell Biology. 151 (3): 601-12 ...
In some cases, the virus with an envelope will form an endosome within the host cell. There are three main types of viral ... "Fusion of Enveloped Viruses in Endosomes." Traffic (Copenhagen, Denmark) vol. 17,6 (2016): 593-614. doi:10.1111/tra.12389 ...
The location of membrane fusion-at the plasma membrane or in endosomes-may vary based on the availability of these triggers for ... White, Judith M.; Whittaker, Gary R. (June 2016). "Fusion of Enveloped Viruses in Endosomes". Traffic. 17 (6): 593-614. doi: ... with some able to enter at the plasma membrane and others entering from endosomes after endocytosis. The interaction of the ... with additional contributions from cysteine proteases cathepsin B and cathepsin L in endosomes. Trypsin and trypsin-like ...
... preferentially binds to early endosomes; fluorescent-labelled dextran can be used to visualize these endosomes under a ...
Wells, W. A. (2007). "Ira Mellman: From endosomes to industry". The Journal of Cell Biology. 177 (4): 570-571. doi:10.1083/jcb. ... Ira Mellman is an American cell biologist who discovered endosomes. He serves as Vice President of Research Oncology at ... Cohn at Rockefeller University and started characterizing endosomes. He returned to Yale after completing postdoctoral work and ...
White, Judith M.; Whittaker, Gary R. (June 2016). "Fusion of Enveloped Viruses in Endosomes". Traffic. 17 (6): 593-614. doi: ...
Raiborg C, Bache KG, Mehlum A, Stang E, Stenmark H (2001). "Hrs recruits clathrin to early endosomes". EMBO J. 20 (17): 5008-21 ... "FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes". J. Cell Sci. 114 (Pt 12): 2255-63 ... "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes". J. Biol. Chem. 278 (14): 12513-21. ... is localized to the cytoplasmic surface of early endosomes". J. Biol. Chem. 272 (33): 20538-44. doi:10.1074/jbc.272.33.20538. ...
Raiborg, C; Bache K G; Mehlum A; Stang E; Stenmark H (Sep 2001). "Hrs recruits clathrin to early endosomes". EMBO J. 20 (17): ...
... which is known to block the v-type H+-ATPases of endosomes. This reduces the acidity in endosomes. The physiological uptake ... Having an acidic endosome pH leads to topological alterations of TcdB (Figure 6). The gene that encodes the TcdB protein, tcdB ... To see whether effects of proteolytic cleavage of TcdB takes place at the cell surface or in acidic endosomes, studies used ... Acidic endosomes allow toxin B to enter the cytosol. This phenomenon takes place by a binding receptor region, which enables ...
20 March 2013). "Conformational biosensors reveal GPCR signalling from endosomes". Nature. 495 (7442): 534-538. Bibcode: ...
... endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes". The Journal of Biological ...
Seemann J, Weber K, Gerke V (August 1997). "Annexin I targets S100C to early endosomes". FEBS Letters. 413 (1): 185-90. doi: ...
... RNAi also disperse endosomes and lysosomes. Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for ...
Park, M. (24 September 2004). "Recycling Endosomes Supply AMPA Receptors for LTP". Science. 305 (5692): 1972-1975. Bibcode: ...
"Conformational biosensors reveal GPCR signalling from endosomes". Nature. 495 (7442): 534-538. Bibcode:2013Natur.495..534I. doi ...
For the movement of the virus in endosomes, Ca2+ is necessary. As NAADP regulates maturation of endosomes by the calcium ... The TPC mechanism once again allows the efflux 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 ... The influx of calcium is what regulates the fusion between the endosome and lysosomes and what mediates trafficking events. ...
Recycling endosomes within the dendritic spine contain pools of AMPA receptors for such synaptic reinsertion. Two distinct ... Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD (September 2004). "Recycling endosomes supply AMPA receptors for LTP". ... October 2008). "Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity". Cell. 135 (3): 535-48 ...
In p14 deficiency cells, the average peri-nuclear distance of late-endosomes increases, indicating most of the late-endosomes ... After endocytosis occurs, early endosomes will mature to late endosomes which will travel towards the peri-nuclear space, where ... Huotari, Jatta; Helenius, Ari (2011-08-31). "Endosome maturation: Endosome maturation". The EMBO Journal. 30 (17): 3481-3500. ... Without p14 protein, the MP1-MAPK- signaling module will not be able to localize to late endosomes, hindering MAPK activation. ...
Viral particles are then transported to late endosomes. Gc-mediated membrane fusion with the endosomal membrane, triggered by ...
"Syntaxin 7 is localized to late endosome compartments, associates with Vamp 8, and Is required for late endosome-lysosome ... Nakamura N, Yamamoto A, Wada Y, Futai M (March 2000). "Syntaxin 7 mediates endocytic trafficking to late endosomes". The ... "A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function". The EMBO ... "A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function". The EMBO ...
... as in early endosomes and recycling endosomes), or sort them to degradation (as in late endosomes and lysosomes). The principal ... Stoorvogel W, Strous GJ, Geuze HJ, Oorschot V, Schwartz AL (May 1991). "Late endosomes derive from early endosomes by ... Late endosomes receive endocytosed material en route to lysosomes, usually from early endosomes in the endocytic pathway, from ... Early endosomes are often located in the periphery of the cell, and receive most types of vesicles coming from the cell surface ...
Mucolipin1 is thought to be localized in endosomes. An important property of mucolipin1 is that decreasing pH (acidification) ...
... J Biol Chem. 2018 Jul 27;293( ... The localizations of Drp1ABCD at lysosomes, late endosomes, and the plasma membrane require two exons, A and B, that are ... Experiments using lysosomal inhibitors show that the association of Drp1ABCD with lysosomes/late endosomes depends on lysosomal ... Furthermore, Drp1ABCD is concentrated at the interorganelle interface between mitochondria and lysosomes/late endosomes. ...
N+ endosomes; and/or motile E−/N+ vesicles fuse with EEA1+ endosomes. E+N+ endosomes can convert to E−/N+ endosomes by ... N+ endosomes and/or motile E−/N+ vesicles fuse with stationary EEA1+ endosomes. Subsequently, E+N+ endosomes are consumed by ... N+ endosome. In addition, events consistent with the fusion of motile NEEP21-positive endosomes with stationary endosomes could ... E+ endosomes devoid of endocytosed NgCAM also showed changes in EEA1 intensity: 15 of 34 (44%) E+ endosomes decreased EEA1 ...
Late Endosome Marker used in Immunocytochemistry/ Immunofluorescence. Abcam provides excellent in-house scientific support ... Immunocytochemistry/ Immunofluorescence abreview for Anti-Rab9 antibody [EPR13272] - Late Endosome Marker. Average ...
ZEBOV uptake is a macropinocytosis-like process that delivers the virus to early endosomes and subsequently to late endosomes. ...
Palabras clave: ARF6 , DEVELOPMENT , ENDOSOMAL PATHWAY , NEURONAL DEVELOPMENT , RAB11 , RAB35 , RABS , RECYCLING ENDOSOME ... The recycling endosome (RE) is a key vesicular component involved in endocytic recycling. Recycling back to the cell surface ... The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All?. .noexiste{ color: #000; } .imagenItem{background- ... Rozés Salvador, María Victoria; González Billault, Christian; Conde, Cecilia Beatriz; The Recycling Endosome in Nerve Cell ...
Wiring innate immunity for a coordinated mobilization of endosomes, autophagosomes and the apoptotic machinery in tumor cells ...
In support for this, we identified a role for SLC15A4, an oligopeptide transporter expressed in early endosomes, in Nod1- ... In support for this, we identified a role for SLC15A4, an oligopeptide transporter expressed in early endosomes, in Nod1- ... pH-dependent Internalization of Muramyl Peptides from Early Endosomes Enables Nod1 and Nod2 Signaling ... Download PDF pH-dependent Internalization of Muramyl Peptides from Early Endosomes Enables Nod1 and Nod2 Signaling. Item ...
Besteiro, S. and Williams, R.A. and Morrison, L.S. and Coombs, G.H. and Mottram, J.C. (2006) Endosome sorting and autophagy are ... Endosome sorting and autophagy are essential for differentiation and virulence of Leishmania major ... The defect in late endosome-autophagosome function in the VPS4E235Q parasites made them less able to withstand starvation than ... developmental biology, endosome sorting, autophagy, Leishmania major, Pharmacy and materia medica, Biochemistry, Cell Biology, ...
Ub-misfolded nascent CFTR [late endosome lumen] (Homo sapiens) * Ub [late endosome lumen] (Homo sapiens) * UBB(1-76) [late ... PL:HSPA8:Autophagy substrate [late endosome lumen] (Homo sapiens) * HSPA8 bound autophagic substrates [late endosome lumen] ( ... PolyUb-Misfolded Proteins:HDAC6 [late endosome lumen] (Homo sapiens) * PolyUb-Misfolded Proteins [late endosome lumen] (Homo ... Substrates for chaperone mediated autophagy [late endosome lumen] (Homo sapiens) * Poly-vimentin:PolyUb-Misfolded Proteins: ...
Mark Cooper, PhD - LDN, Endosomes and the Nanophysilogy of Autoimmune Movement Disorders II (2019 Conference) (LDN, low dose ... Mark Cooper, PhD - LDN, Endosomes and the Nanophysiology of Autoimmune Movement Disorders II (2019 Conference) (LDN, low dose ... Mark Cooper, PhD - LDN, Endosomes and the Nanophysilogy of Autoimmune Movement Disorders II (2019 Conference) (LDN, low dose ...
... are transported from endosomes to the Golgi after delivering lysosomal enzymes to the endocytic pathway. This process requi ... Thus, MPRs may travel from early endosomes to recycling endosomes to late endosomes en route to the Golgi complex. We focus on ... To verify that STX10 is required at the TGN for the receipt of late endosome but not early endosome-derived cargoes, we tested ... 4, C and D). A significant proportion of sorting nexin-2 protein colocalizes with early endosome markers such as early endosome ...
activated TLR4:TRIF:K63polyUb-TRAF3:K63polyUb-TANK:p-TBK1/p-IKKE:IRF3/IRF7 [endosome membrane] Stable Identifier ... activated TLR4:TRIF:K63polyUb-TRAF3:K63polyUb-TANK:p-TBK1/p-IKKE:IRF3/IRF7 [endosome membrane] (Homo sapiens) ... activated TLR4:TRIF:K63polyUb-TRAF3:K63polyUb-TANK:p-TBK1/p-IKKE:IRF3/IRF7 [endosome membrane] (Homo sapiens) ... activated TLR4:TRIF:K63polyUb-TRAF3:K63polyUb-TANK:p-TBK1/p-IKKE:IRF3/IRF7 [endosome membrane] (Bos taurus) ...
Uncoating of influenza virus in endosomes. / Yoshimura, A.; Ohnishi, S. I.. In: Journal of Virology, Vol. 51, No. 2, 1984, p. ... Yoshimura, A., & Ohnishi, S. I. (1984). Uncoating of influenza virus in endosomes. Journal of Virology, 51(2), 497-504. https ... Yoshimura, A. ; Ohnishi, S. I. / Uncoating of influenza virus in endosomes. In: Journal of Virology. 1984 ; Vol. 51, No. 2. pp ... Uncoating of influenza virus in endosomes」の研究トピックを掘り下げます。これらがま
Endosomes Fibroblasts Fluorescent Dyes HeLa Cells Humans Lysosomes Membrane Glycoproteins Microscopy, Fluorescence Protein ... Title : Endosome motility defects revealed at super-resolution in live cells using HIDE probes Personal Author(s) : Gupta, ... Endosome motility defects revealed at super-resolution in live cells using HIDE probes. ... In wild-type fibroblasts, the probes reveal distinct but rare inter-endosome kiss-and-run events that cannot be observed using ...
Hoekstra, D. ; Rejman, J. ; Wasungu, L. ; Shi, F. ; Zuhorn, I. / Gene delivery by cationic lipids : in and out of an endosome. ... Hoekstra, D, Rejman, J, Wasungu, L, Shi, F & Zuhorn, I 2007, Gene delivery by cationic lipids: in and out of an endosome, ... Gene delivery by cationic lipids : in and out of an endosome. / Hoekstra, D.; Rejman, J.; Wasungu, L.; Shi, F.; Zuhorn, I. ... Gene delivery by cationic lipids: in and out of an endosome. D. Hoekstra*, J. Rejman, L. Wasungu, F. Shi, I. Zuhorn ...
View mouse Ints14 Chr9:64868187-64894260 with: sequences, polymorphisms, proteins, references, function, expression
In the endosome section the acid DNase activity was up to ten times higher than in the cortex and the presence of DNase II-like ... deoxyribonucleases, cortex, endosome; marine sponge; Tethya aurantium; acid DNase; neutral DNase. Subjects:. NATURAL SCIENCES ... The presence and activity of deoxyribonucleases in the cortex and endosome sections from a sponge, the sea orange Tethya ... Deoxyribonucleases (DNases) in the cortex and endosome from marine sponge Tethya aurantium ...
Inclusion sequestration impairs endosome maturation In mice, a neurodegenerative pathway involving Tbk1 gene mutations and ... chromosome 9 open reading frame 72 repeat expansions impairs endosome maturation and induces cytoplasmic TBP-43 aggregation. ...
The importance of endosome-to-trans-Golgi network (TGN) retrograde transport in the anterograde transport of proteins is ... Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport. Molecular Biology of the Cell. ... Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also ... Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also ...
Identification and characterization of lipids from endosomes purified by electromagnetic chromatography.. Authors: Guha, Sonia ... Here, we have used a magnetic chromatography technique to isolate the endosomes from rat peritoneal macrophages and studied ... The data suggested that both early and late endosomes were rich in cholesterol, whereas sphingomyelin (SM) and specific ... The endosomal purification method described here yields pure endosomes with little or no contamination from mitochondria and ...
... which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell ... which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell ... VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell ... VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell ...
Cargo sorting on endosomes. The distinguishing feature of the sorting endosome is its ability to direct cargo towards recycling ... 5P and PI4P as they transition to late endosomes [29]. The architecture of the sorting endosome lends itself towards sorting ... The ESCRT-0 component HRS is required for WASH presence on endosomes as is the tail of FAM21 that can bind the retromer complex ... The first ESCRT subcomplex to be recruited to endosomes is ESCRT-0 which is composed of HRS and STAM [71]. HRS recruitment is ...
EVs can be derived from multivesicular endosomes (MVEs) or from budding at the plasma membrane. Endosomes bud inwards during ... endosome exosome extracellular vesicles fungal RNA biology membrane trafficking RNA recognition motif RNA transport 2020-01-23 ... Tagged with: endosome exosome extracellular vesicles fungal RNA biology membrane trafficking RNA recognition motif RNA ... Inside-out - from endosomes to extracellular vesicles in fungal RNA transport. in Publications January 23, 2020 ...
Plant Endosome Enrichment Kit has been developed using a spin-column-based format coupling with selective precipitation for ... Detection of Enriched Endosomes from N. benthmiana by Western blotting. The plant leaf that carries GFP-tagged ara6 (early ... Endosomes are a heterogeneous collection of organelles in the sorting and delivery of internalized material from cell surface ... In plant cells, two clearly defined endosomal compartments have been identified: the trans-Golgi network (early endosome ...
Calcium-containing endosomes at oculomotor terminals in animal models of ALS. NeuroReport. 1999 Aug 20;10(12):2539-2545. https ... Calcium-containing endosomes at oculomotor terminals in animal models of ALS. In: NeuroReport. 1999 ; Vol. 10, No. 12. pp. 2539 ... Calcium-containing endosomes at oculomotor terminals in animal models of ALS. László Siklós, József I. Engelhardt, Róbert ... Calcium-containing endosomes at oculomotor terminals in animal models of ALS. / Siklós, László; Engelhardt, József I.; Adalbert ...
Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range ... We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal ... Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase ... Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell ...
... in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a ... In these endosomes, we could localize the ALK1-Endoglin complex, labeled BMP9 as well as SMAD1, highlighting Caveolin-1 ... Atheroprone fluid shear stress-regulated ALK1-Endoglin-SMAD signaling originates from early endosomes Authors: ... in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a ...
Biomarkers of Errant Endosome Spotted in Cerebrospinal Fluid Posted By Alz Forum. On 09/12/2020 @ 9:00 am In Science , No ... 1] Read the article in full on the Alz Forum Website: https://www.alzforum.org/news/research-news/biomarkers-errant-endosome- ... URL to article: https://www.dementiaresearcher.nihr.ac.uk/biomarkers-of-errant-endosome-spotted-in-cerebrospinal-fluid/ ...
The virions aggregate in the large endosomes (cytoplasmic vesicles). The viral membranes fuse to the endosomal membranes, ...
Davies CW, Paul LN, Das C. Mechanism of recruitment and activation of the endosome-associated deubiquitinase AMSH. Biochemistry ...
  • VPS4E235Q accumulated in vesicles from the endocytic pathway, and the mutant L. major was deficient in endosome sorting. (strath.ac.uk)
  • Researchers from Heinrich Heine University Düsseldorf review the RNA cargo and mechanistic details of transport via two inter-related sets of organelles: endosomes and extracellular vesicles for intra- and intercellular RNA transfer. (exosome-rna.com)
  • Endosomes bud inwards during maturation to form intraluminal vesicles, incorporating contents from the cytosol, notably sRNAs and proteins. (exosome-rna.com)
  • Kwon S, Tisserant C, Tulinski M, Weiberg A, Feldbrügge, M. (2010) Inside-Out: From Endosomes to Extracellular Vesicles in Fungal RNA Transport . (exosome-rna.com)
  • In these endosomes, we could localize the ALK1-Endoglin complex, labeled BMP9 as well as SMAD1, highlighting Caveolin-1 vesicles as a SMAD signaling compartment in cells exposed to low atheroprone laminar shear stress. (abberior.rocks)
  • The virions aggregate in the large endosomes (cytoplasmic vesicles). (cdc.gov)
  • RME-1 family proteins are normally found in close association with recycling endosomes and the vesicles and tubules emanating from these endosomes, consistent with the proposal that these proteins directly participate in endosomal transport. (wormbase.org)
  • One model would be that the large vacuoles are derived from the small vesicles and reflect a defect in endosome sorting which results in a mild reduction of YP170-GFP uptake by rme-1 mutants. (wormbase.org)
  • The protein VPS35, the main component of the retromer, mediates the maturation of early endosomes into late autophagy vesicles, where degradation and recycling ultimately take place," said Pla-Martin. (phys.org)
  • High resolution image of the largest accumulation of endosomal vesicles and early endosomes is next to the buccal cavity area under the membranelles of the peniculi and quadrulus. (ucsd.edu)
  • Vesicles and early endosomes under the membranelles of the peniculus of the buccal cavity. (ucsd.edu)
  • The shaped endocytic vesicles fuses with the early endosomes within the peripheral cytoplasm (Nour and Modis, 2014). (achengula.com)
  • Intriguingly, neurons express cell type-specific proteins that localize to endosomes, but little is known about how these neuronal proteins interface with canonical endosomes and ubiquitously expressed endosomal components, such as EEA1 (Early Endosomal Antigen 1). (jneurosci.org)
  • NEEP21 (Neuronal Early Endosomal Protein 21 kDa) localizes to somatodendritic endosomes, and downregulation of NEEP21 perturbs the correct trafficking of multiple receptors, including glutamate receptors (GluA2) during LTP and amyloidogenic processing of βAPP. (jneurosci.org)
  • Last, we uncover evidence that functional interference with NEEP21 reduces axon and dendrite growth of primary rat hippocampal neurons on L1 substrate but not on N-cadherin substrate, thus implicating endosomal trafficking through somatodendritic early endosomes in L1-mediated axon growth. (jneurosci.org)
  • Given the crucial cargos affected by NEEP21, we set out to uncover how neuronal early endosomes containing the ubiquitously expressed EEA1 (Early Endosomal Antigen 1) and/or NEEP21 were dynamically organized, and whether EEA1 and/or NEEP21 affected L1-mediated axon outgrowth. (jneurosci.org)
  • The endosomal purification method described here yields pure endosomes with little or no contamination from mitochondria and hence could be used for further biochemical and marker analysis, giving insight into mechanisms of endocytic traffic. (who.int)
  • We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. (ox.ac.uk)
  • Subsequently, it has emerged that endocytosis is also required for the maintenance of cellular plasticity [ 2 ] and that endosomes can provide an important signalling platform, as activated receptors continue to signal and recruit downstream adapters to endosomal membranes [ 3 ]. (portlandpress.com)
  • In plant cells, two clearly defined endosomal compartments have been identified: the trans-Golgi network (early endosome equivalent) and the multivesicular body (late endosome equivalent). (inventbiotech.com)
  • Further analysis of APPL1-positive endosomes showed that, similar to Rab5-endosomes, they display more frequent long-range retrograde than anterograde movement, with the endosomal levels of APPL1 correlated with faster retrograde movement. (scitok.com)
  • Mannose 6-phosphate receptors (MPRs) are transported from endosomes to the Golgi after delivering lysosomal enzymes to the endocytic pathway. (rupress.org)
  • We show in human cells that a soluble NSF attachment protein receptor (SNARE) complex comprised of syntaxin 10 (STX10), STX16, Vti1a, and VAMP3 is required for this MPR transport but not for the STX6-dependent transport of TGN46 or cholera toxin from early endosomes to the Golgi. (rupress.org)
  • Thus, MPRs may travel from early endosomes to recycling endosomes to late endosomes en route to the Golgi complex. (rupress.org)
  • The importance of endosome-to-trans-Golgi network (TGN) retrograde transport in the anterograde transport of proteins is unclear. (elsevier.com)
  • In this study, genome-wide screening of the factors necessary for efficient anterograde protein transport in human haploid cells identified subunits of the Golgi-associated retrograde protein (GARP) complex, a tethering factor involved in endosome-to-TGN transport. (elsevier.com)
  • Therefore GARP-and VAMP4-dependent endosome-to-TGN retrograde transport is required for recycling of molecules critical for efficient post-Golgi anterograde transport of cell-surface integral membrane proteins. (elsevier.com)
  • Endosomes are a heterogeneous collection of organelles in the sorting and delivery of internalized material from cell surface and the transport of materials from Golgi to lysosome or vacuole. (inventbiotech.com)
  • We demonstrate that IFT20 is required for the association of ATG16L1 with the Golgi complex and early endosomes, both of which have been identified as membrane sources for phagophore elongation. (uniroma3.it)
  • This involves the ability of IFT20 to interact with proteins that are resident at these subcellular localizations, namely the golgin GMAP210 at the Golgi apparatus and Rab5 at early endosomes. (uniroma3.it)
  • Secondly, after being shuttled to an endosome, the ricin is delivered to the Golgi apparatus, from which it makes its way to the cellular cytosol, where it begins its deactivation of ribosomes. (cdc.gov)
  • It is also required for the transport of the MANNOSE-6-PHOSPHATE RECEPTOR from endosomes to the TRANS-GOLGI NETWORK. (bvsalud.org)
  • This Drp1 isoform is termed Drp1 ABCD because it contains four alterative exons: A, B, C, and D. Remarkably, Drp1 ABCD is located at lysosomes, late endosomes, and the plasma membrane in addition to mitochondria. (nih.gov)
  • The localizations of Drp1 ABCD at lysosomes, late endosomes, and the plasma membrane require two exons, A and B, that are present in the GTPase domain. (nih.gov)
  • Endocytosis occurs through a variety of clathrin dependent and independent mechanisms (discussed in detail in other reviews [ 4-6 ]), where lipids and transmembrane proteins are internalised from the plasma membrane into vesicular structures called early or sorting endosomes. (portlandpress.com)
  • Internalised cargo from the plasma membrane reaches the sorting endosome stage from which it can be transported to one of three destinations. (portlandpress.com)
  • EVs can be derived from multivesicular endosomes (MVEs) or from budding at the plasma membrane. (exosome-rna.com)
  • Members of the RME-1/mRme-1/EHD1 protein family have recently been shown to function in the recycling of membrane proteins from recycling endosomes to the plasma membrane. (wormbase.org)
  • Overexpression of VAMP4, v-SNARE, in VPS54-KO cells partially restored not only endosome-to-TGN retrograde transport, but also anterograde transport of both GPI-anchored and transmembrane proteins. (elsevier.com)
  • By labeling neighboring proteins-so-called proximity labeling-we showed that mtDNA damage leads to the recruitment of endosomes in close proximity to nucleoids. (phys.org)
  • The subcellular distribution of the proteins Rab5a and syntaxin-4 suggested a role in docking of granules and/or endosomes to the target membrane in the neutrophil. (biologists.com)
  • These compartments, called endosomes, traffic proteins throughout cells. (drugtargetreview.com)
  • Exosomes form through invagination of endosomes to encapsulate cytoplasmic contents, and upon fusion of these multivesicular endosomes to the cell surface, exosomes are released to the extracellular space and transport mRNA, microRNA (miRNA) and proteins between cells. (northwestern.edu)
  • Furthermore, Drp1 ABCD is concentrated at the interorganelle interface between mitochondria and lysosomes/late endosomes. (nih.gov)
  • Experiments using lysosomal inhibitors show that the association of Drp1 ABCD with lysosomes/late endosomes depends on lysosomal pH but not their protease activities. (nih.gov)
  • These results indicate the uncoating of influenza virus in endosomes before reaching the secondary lysosomes. (elsevier.com)
  • It has been known that Wortmannin inhibits the recycling of endosomes or transition to lysosomes and causes enlargement of endosomes. (dojindo.com)
  • To evaluate these changes caused by Wortmannin, early endosomes were co-stained by ECGreen and Rab5-RFP (marker protein of early endosomes), and lysosomes were co-stained by ECGreen and lysosome staining reagent. (dojindo.com)
  • In neutrophils, this occurs via sequential fusions with early and late endosomes and finally lysosomes, thus yielding a phagolysosome. (medscape.com)
  • Immunofluorescence with anti-RME-1 Abs shows that RME-1 is a cytoplasmic protein expressed in all cells, and that it is associated with the periphery of basolateral endosomes in the wild-type intestine. (wormbase.org)
  • Ari Helenius was the primary individual to show that some enveloped viruses fuse with the endosomes to ship their genome into the cytosol (Helenius et al. (achengula.com)
  • 2018). The low pH for fusion varies between viruses making some viruses to fuse both throughout early endosomes (comparatively excessive pH ∼ 6.0) or late endosomes (low pH ∼ 5) to launch its content material to the cytosol (White and Whittaker, 2016). (achengula.com)
  • This finding, that transformation to the infective metacyclic form is dependent on late endosome function and, more directly, autophagy, makes L. major a good model for studying the roles of these processes in differentiation. (strath.ac.uk)
  • Efficient cross-presentation requires antigen uptake-mediated entrance of antigen into early endosome [ 12 ], which was mediated by mannose receptor [ 13 ]. (hindawi.com)
  • The recycling endosome (RE) is a key vesicular component involved in endocytic recycling. (conicet.gov.ar)
  • However, MPRs cannot release their bound ligands upon arrival in early endosomes because they require a lower pH than typical endocytic receptors for efficient ligand release ( Tong and Kornfeld, 1989 ). (rupress.org)
  • Both clathrin dependent and also clathrin-independent endocytosis mechanisms such as the CLIC-GEEC (clathrin-independent carriers/GPI-anchored enriched compartments) pathway or marcopinocytosis are thought to eventually merge with early sorting endosomes [ 11 ]. (portlandpress.com)
  • Mechanistically, we reveal that long-term exposure of ECs to low laminar shear stress leads to enhanced Endoglin expression and endocytosis of Endoglin in Caveolin-1-positive early endosomes. (abberior.rocks)
  • The visualization of endocytosis using the ECGreen is a more direct method than fluorescent analogs and allows visualization endocytosis from the stage of early endosomes. (dojindo.com)
  • rme-1 which appears to function in the endosome, and rme-8 which appears to function early in endocytosis. (wormbase.org)
  • The acidic pH within the endosomes tends to extend by means of the totally different phases of endosomes in direction of maturity (Hu et al. (achengula.com)
  • The key feature of the cholesterol-dependent toxin listeriolysin O mutant (LLO Y406A) is its preferential activity at pH 5.7, which could be exploited either directly for selective targeting of cancer cells or the release of accumulated therapeutics from acidic endosomes. (dissem.in)
  • In addition, ATP depletion caused RME-1 to lose its endosome association in the cell, resulting in cytosolic localization. (wormbase.org)
  • We identified Endoglin to be essential in preventing excessive activation of SMAD1/5 under physiological flow conditions and Caveolin-1-positive early endosomes as a new flow-regulated signaling compartment for BMP9-ALK1-Endoglin signaling axis in atheroprone flow conditions. (abberior.rocks)
  • Here, we characterized the motility of Rab5 endosomes in primary cultures of mouse hippocampal pyramidal cells by live-cell imaging and showed that they exhibit bi-directional long-range motility in axons, with a strong bias toward retrograde transport. (scitok.com)
  • We conclude that Rab5-APPL1 endosomes exhibit the hallmarks of axonal signaling endosomes to transport Akt1 in hippocampal pyramidal cells. (scitok.com)
  • Conversely, IFT20 was found to recruit ATG16L1 to early endosomes tagged for autophagosome formation by the BECLIN 1/VPS34/Rab5 complex, which resulted in the local accumulation of LC3. (uniroma3.it)
  • In adding Wortmannin, ECGreen was colocalized with enlarged endosomes (Rab5-RFP). (dojindo.com)
  • The defect in late endosome-autophagosome function in the VPS4E235Q parasites made them less able to withstand starvation than wild-type L. major. (strath.ac.uk)
  • supports a model in which MPRs travel through late endosomes before arrival at the TGN. (rupress.org)
  • The data suggested that both early and late endosomes were rich in cholesterol, whereas sphingomyelin (SM) and specific phospholipids like phosphatidylcholine. (who.int)
  • Trafficking through the late endosome significantly impacts candida albicans tolerance of the azole antifungals. (unisucre.edu.co)
  • Trafficking studies of these LNPs showed strong localization with late endosomes. (biorxiv.org)
  • Early endosomes containing the virus are transported in direction of the nucleus on microtubules the place in between they mature to late endosomes (Le Blanc et al. (achengula.com)
  • The modifications from early endosomes to late matured endosomes includes development of dimension because of acquired cargo on transit and newly synthesized elements and alter in pH, lipid and protein composition. (achengula.com)
  • Hence IFT20 participates in autophagosome biogenesis under basal conditions by regulating the localization of ATG16L1 at early endosomes to promote autophagosome biogenesis. (uniroma3.it)
  • NEEP21 dynamically localizes with EEA1-positive early endosomes but is also found in EEA1-negative endosomes. (jneurosci.org)
  • Live imaging reveals that NEEP21-positive, EEA1-negative endosomes arise as a consequence of maturational conversion of EEA1/NEEP21 double-positive endosomes. (jneurosci.org)
  • Annexin VI has been implicated in mediating the endosome aggregation and vesicle fusion in secreting epithelia during exocytosis. (creativebiomart.net)
  • IMSEAR at SEARO: Identification and characterization of lipids from endosomes purified by electromagnetic chromatography. (who.int)
  • Overexpression of TMEM87A or its close homologue TMEM87B in VPS54-KO cells partially restored endosome-to-TGN retrograde transport and anterograde transport. (elsevier.com)
  • In addition, TMEM87A and TMEM87B are involved in endosome-to-TGN retrograde transport. (elsevier.com)
  • Interestingly, APPL1-endosomes transport the neurotrophin receptor TrkB and mediate retrograde axonal transport of the kinase Akt1. (scitok.com)
  • Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes. (bioss.com.cn)
  • Here, we have used a magnetic chromatography technique to isolate the endosomes from rat peritoneal macrophages and studied their lipid composition. (who.int)
  • Because fluid-phase markers like dextran can enter the recycling pathway, and FM4-64 does not, rme-1 mutant vacuoles may represent aberrant recycling endosomes. (wormbase.org)
  • In contrast to macrophages, neutrophils differ in the contents of these endosomes. (medscape.com)
  • Using border cells in the Drosophila ovary as a model system for collective migration, we found that the receptor tyrosine kinase (RTK) PDGF/VEGF receptor (PVR) is required for a polarized distribution of recycling endosome and exocyst in the leading cells of the border cell cluster. (silverchair.com)
  • Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). (bioss.com.cn)
  • Simultaneous transport and translation of messenger RNAs (mRNAs) on the surface of shuttling endosomes is a conserved process pertinent to highly polarised eukaryotic cells, such as hyphae or neurons. (exosome-rna.com)
  • However, they have limitations in observing dynamics of endosomes in live cells in terms of precision of staining or retentivity of reagent. (dojindo.com)
  • The RE consists of a network of interconnected and functionally distinct tubular subdomains that originate from sorting endosomes and transport their cargoes along microtubule tracks, by fast or slow recycling pathways. (conicet.gov.ar)
  • Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. (ox.ac.uk)
  • VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. (ox.ac.uk)
  • The function of endosomes is intricately linked to cellular function in all cell types, including neurons. (jneurosci.org)
  • The plant leaf that carries GFP-tagged ara6 (early endosome marker) was processed as described in the protocol and probed with anti-ara6 and anti-histone antibodies. (inventbiotech.com)
  • Davies CW, Paul LN, Das C. Mechanism of recruitment and activation of the endosome-associated deubiquitinase AMSH. (medlineplus.gov)
  • In support for this, we identified a role for SLC15A4, an oligopeptide transporter expressed in early endosomes, in Nod1-dependent NF-kappaB signaling. (uzh.ch)
  • The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All? (conicet.gov.ar)
  • Hemin protects against Zika virus infection by disrupting virus-endosome fusion. (bvsalud.org)
  • Subsequently, by fluorescence spectroscopy studies, intracellular fusion assay and syncytia formation assay, we revealed that hemin acts on the process of virus - endosome fusion. (bvsalud.org)
  • This study elaborated that hemin could play anti- ZIKV activity by disrupting the virus - endosome fusion process and shed new light on developing novel agents against ZIKV infection . (bvsalud.org)
  • This review will summarise recent developments regarding the composition and regulation of the recycling machineries and their relationship with the degradative pathways of the endosome. (portlandpress.com)