Endosomes: Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.rab5 GTP-Binding Proteins: A genetically related subfamily of RAB GTP-BINDING PROTEINS involved in transport from the cell membrane to early endosomes. This enzyme was formerly listed as EC 3.6.1.47.rab GTP-Binding Proteins: A large family of MONOMERIC GTP-BINDING PROTEINS that play a key role in cellular secretory and endocytic pathways. EC 3.6.1.-.Lysosomes: A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Vesicular Transport Proteins: A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.trans-Golgi Network: 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.rab4 GTP-Binding Proteins: 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.Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the MITOCHONDRIA; the GOLGI APPARATUS; ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Transferrin: 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.Clathrin: The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.Receptors, Transferrin: 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.Endosomal Sorting Complexes Required for Transport: A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.Golgi Apparatus: A stack of flattened vesicles that functions in posttranslational processing and sorting of proteins, receiving them from the rough ENDOPLASMIC RETICULUM and directing them to secretory vesicles, LYSOSOMES, or the CELL MEMBRANE. The movement of proteins takes place by transfer vesicles that bud off from the rough endoplasmic reticulum or Golgi apparatus and fuse with the Golgi, lysosomes or cell membrane. (From Glick, Glossary of Biochemistry and Molecular Biology, 1990)Cell Compartmentation: A partitioning within cells due to the selectively permeable membranes which enclose each of the separate parts, e.g., mitochondria, lysosomes, etc.Multivesicular Bodies: Endosomes containing intraluminal vesicles which are formed by the inward budding of the endosome membrane. Multivesicular bodies (MVBs) may fuse with other organelles such as LYSOSOMES or fuse back with the PLASMA MEMBRANE releasing their contents by EXOCYTOSIS. The MVB intraluminal vesicles released into the extracellular environment are known as EXOSOMES.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Transport Vesicles: Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations.Receptor, IGF Type 2: A receptor that is specific for IGF-II and mannose-6-phosphate. The receptor is a 250-kDa single chain polypeptide which is unrelated in structure to the type 1 IGF receptor (RECEPTOR, IGF TYPE 1) and does not have a tyrosine kinase domain.Sorting Nexins: 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.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Membrane Fusion: The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes.Lysosome-Associated Membrane Glycoproteins: Ubiquitously expressed integral membrane glycoproteins found in the LYSOSOME.Clathrin-Coated Vesicles: 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.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Intracellular Membranes: Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.Adaptor Protein Complex 1: A clathrin adaptor protein complex primarily involved in clathrin-related transport at the TRANS-GOLGI NETWORK.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Brefeldin A: A fungal metabolite which is a macrocyclic lactone exhibiting a wide range of antibiotic activity.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Monoglycerides: GLYCEROL esterified with a single acyl (FATTY ACIDS) chain.Qa-SNARE Proteins: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Microscopy, Confocal: A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology.ADP-Ribosylation Factors: 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 3.6.1.47Phagosomes: 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.Green Fluorescent Proteins: 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.Adaptor Protein Complex gamma Subunits: 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.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Microscopy, Immunoelectron: Microscopy in which the samples are first stained immunocytochemically and then examined using an electron microscope. Immunoelectron microscopy is used extensively in diagnostic virology as part of very sensitive immunoassays.Subcellular Fractions: Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Protein Binding: 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 Fusion Proteins: 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.Adaptor Proteins, Vesicular Transport: 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.Coated Pits, Cell-Membrane: 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.R-SNARE Proteins: 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).Virus Internalization: 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.Cell Fractionation: Techniques to partition various components of the cell into SUBCELLULAR FRACTIONS.Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.Cathepsin D: An intracellular proteinase found in a variety of tissue. It has specificity similar to but narrower than that of pepsin A. The enzyme is involved in catabolism of cartilage and connective tissue. EC 3.4.23.5. (Formerly EC 3.4.4.23).Androstenes: Unsaturated derivatives of the steroid androstane containing at least one double bond at any site in any of the rings.Protein Structure, Tertiary: 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, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Phosphatidylinositol Phosphates: Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.CHO Cells: 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.Asialoglycoproteins: Endogenous glycoproteins from which SIALIC ACID has been removed by the action of sialidases. They bind tightly to the ASIALOGLYCOPROTEIN RECEPTOR which is located on hepatocyte plasma membranes. After internalization by adsorptive ENDOCYTOSIS they are delivered to LYSOSOMES for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with HEPATIC CIRRHOSIS or HEPATITIS.Adaptor Protein Complex 3: An adaptor protein complex found primarily on perinuclear compartments.Models, Biological: 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.Vesicle-Associated Membrane Protein 3: 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.Cercopithecus aethiops: 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.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mutation: 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.Cytoplasmic Vesicles: Membrane-limited structures derived from the plasma membrane or various intracellular membranes which function in storage, transport or metabolism.COS Cells: 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).)Pinocytosis: The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Cell Polarity: 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.Dynamins: 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.Transfection: 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.Luminescent Proteins: 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, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Microtubules: 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.Lysosomal-Associated Membrane Protein 1: 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.Signal Transduction: 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.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Annexin A2: 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.Vacuolar Proton-Translocating ATPases: Proton-translocating ATPases that are involved in acidification of a variety of intracellular compartments.RNA, Small Interfering: 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: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Fluorescent Antibody Technique: 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.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Dyneins: 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.PC12 Cells: 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.SNARE Proteins: 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.)Cytosol: Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.RNA Interference: 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.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Lysosomal-Associated Membrane Protein 2: An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. Loss of expression of lysosomal-associated membrane protein 2 is associated with GLYCOGEN STORAGE DISEASE TYPE IIB.GTP Phosphohydrolases: Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.Receptor, Epidermal Growth Factor: 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.Kinetics: The rate dynamics in chemical or physical systems.Ammonium Chloride: 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 ...
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 ...
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.
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 ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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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 ...
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
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 ...
マウス・モノクローナル抗体 ab70521 交差種: Hu 適用: ICC/IF…EEA1抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
Are you suggesting that the protein is being endocytosed rather than expressed in the cultured primary cells? I doubt that would be the case because on fusion of the endosome with a lysosome the proteins in the vesicle are usually degraded by the lysosomal enzymes. For the protein to enter using endosomes, it would have to either resist proteolytic degradation or prevent fusion of the endosome and lysosome. Further, the protein would have to escape from the endosome if it is to function in the cytosol. It may not be impossible for an intact protein to both survive and escape from the endocytotic pathway, but it is not common ...
Endosomal networks in immunology When a T cell in our immune system gets the right signal it leaps into action within seconds - taking on one of many different roles in fighting the infection. Jérémie Rossy and his group are using single molecule imaging to examine how messages received at the cell surface are transmitted via the membrane and specialised compartments within the cell, such as endosomes.
Polyclonal antibody for SR D1/CD68 detection. Host: Rabbit.Size: 100μg/vial. Tested applications: IHC-P. Reactive species: Mouse. SR D1/CD68 information: Molecular Weight: 34818 MW; Subcellular Localization: Isoform Long: Endosome membrane; Single-pass ty
EEA1 antibody [C3], C-term (early endosome antigen 1) for ICC/IF, IHC-P, WB. Anti-EEA1 pAb (GTX109638) is tested in Human, Mouse, Rat, Hamster samples. 100% Ab-Assurance.
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Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
ROBLD3, 0.1 mg. The late endosomal/lysosomal adaptor MAPK and MTOR activator 2 (LAMTOR2) protein belongs to the LAMTOR family of proteins, and together with LAMTOR3 and the MAPK1 and ERK kise 1 (MEK1) localizes to late endosomes where it is required for
The product of this gene is highly conserved with a mouse protein associated with the cytoplasmic face of late endosomes and lysosomes. The mouse…
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.
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 sorting endosome in the Medical Dictionary? sorting endosome explanation free. What is sorting endosome? Meaning of sorting endosome medical term. What does sorting 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 ...
Endosomal accumulation of APP in wobbler motor neurons reflects impaired vesicle trafficking: Implications for human motor neuron disease ...
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 ...
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.. ...
endosome membrane. Биологический процесс. • negative regulation of transcription from RNA polymerase II promoter. • toll-like ...
Recycling endosomes within the dendritic spine contain pools of AMPA receptors for such synaptic reinsertion.[46] Two distinct ... Park M, Penick EC, Edwards JG, Kauer JA, Ehlers MD (September 2004). "Recycling endosomes supply AMPA receptors for LTP". ... "Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity". Cell. 135 (3): 535-48. doi:10.1016/j. ...
Endosomes. Retinoids, androgens, estrogens. NAD+. Oxidation. Liver, testis, lung, spleen, brain, ovary, kidney, adrenal, ...
... is a complex of proteins that has been shown to be important in recycling transmembrane receptors from endosomes to ... "Retromer: a master conductor of endosome sorting". cshperspectives.cshlp.org/. Cold Spring Harbor Laboratory Press. Retrieved ... Retromer plays a central role in the retrieval of several different cargo proteins from the endosome to the trans-Golgi network ... yeast endosome equivalent) compartment in yeast. It is also required for the recycling of the cell surface receptor CED-1, ...
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 ( ...
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 (2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. 279 (6): 4670-9. doi:10.1074/jbc ... Seet, Li-Fong; Liu Ningsheng; Hanson Brendon J; Hong Wanjin (Feb 2004). "Endofin recruits TOM1 to endosomes". J. Biol. Chem. ...
In turn, parts of the membranes of some endosomes are subsequently internalized as smaller vesicles. Such endosomes are called ... Booth AM, Fang Y, Fallon JK, Yang JM, Hildreth JE, Gould SJ (2006). "Exosomes and HIV Gag bud from endosome-like domains of the ... Endosome Ectosome Microvesicles Membrane vesicle trafficking International Society for Extracellular Vesicles van der Pol E, ... Huotari, J.; Helenius, A. (2011). "Endosome maturation". The EMBO Journal. 30 (17): 3481-3500. doi:10.1038/emboj.2011.286. PMC ...
... 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 ...
... preferentially binds to early endosomes; fluorescent-labelled dextran can be used to visualize these endosomes under a ...
... , Ph.D. is an American cell biologist who discovered endosomes. He serves as Vice President of Research Oncology at ... Mellman plays bass in his own rock band called "The Cellmates." Wells, W. A. (2007). "Ira Mellman: From endosomes to industry ... Cohn at Rockefeller University and started characterizing endosomes. He returned to Yale after completing postdoctoral work and ...
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. England. ...
... 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 ...
"Endosome and INPP4B." Oncotarget. 2016 Jan 5;7(1):5-6. M.S. Song, L. Salmena, A. Carracedo-Perez, A. Egia, F. Lo Coco, J. ... "In vivo role of INPP4B in tumor and metastasis suppression through regulation of PI3K/AKT signaling at endosomes." Cancer ...
Kutateladze, Tatiana; Overduin, Michael (2001). "Structural Mechanism of Endosome Docking by the FYVE Domain". Science. 291 ( ...
... 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 ...
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 influx of calcium for the fusion of the endosomes and lysosomes (where LDL is degraded ... Therefore, when TPCs are not functioning, the Ebolavirus cannot escape before the fusion of the endosome with the lysosome. In ... The influx of calcium is what regulates the fusion between the endosome and lysosomes and what mediates trafficking events. ...
Germination occurs both extracellularly or in type II pneumocyte endosomes containing conidia.[11][14] Following germination, ...
"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 ...
Endosomes, exosomes and Trojan viruses.. Pelchen-Matthews A1, Raposo G, Marsh M. ...
Cells in which HIF-2α was stabilized failed to form giant endosomes upon transfection with an activated form of Rab5, and in ... which is necessary for Rab5-mediated endosome fusion. Forced expression of rabaptin-5 reduced the half-life of EGFR and ...
Late endosomes derive from early endosomes by maturation.. Stoorvogel W1, Strous GJ, Geuze HJ, Oorschot V, Schwartz AL. ... Late endosomes are the major site for entry of newly synthesized lysosomal hydrolases via the cation-independent mannose 6- ... No consensus exists as to the mechanism of transport from early to late endosomes. We used asialoorosomucoid and transferrin to ... These results together with immunoelectron microscopic data support a model in which early endosomes gradually mature into late ...
... Curr Opin Cell Biol. 2002 Aug;14(4):454-62. doi: 10.1016/s0955-0674(02)00352-6. ... that Phox homology domains recognise phosphatidylinositol 3-phosphate explains how sorting nexins are recruited to endosomes, ...
Gene Ontology (GO) annotations for endosome All GO annotations for Grn (62) ...
... a docking protein on the surface of early endosomes. APP seemed to never quite reach the endosome lumen, which is necessary for ... Alzheimers GWAS Hits Point to Endosomes, Synapses. Go to another part. Series - Society for Neuroscience Annual Meeting 2015: ... When he silenced Bin1, BACE1 co-localized more with the early endosome marker Rab5 in axons. The secretase exited much more ... They spotted Bin1 and CD2AP in endosomes, and Bin1 in postsynaptic compartments as well. The sightings suggest that both Bin1 ...
Endosomes comprise three different compartments: early endosomes, late endosomes, and recycling endosomes. They are ... Early endosomes then mature into late endosomes before fusing with lysosomes. Early endosomes mature in several ways to form ... a process that begins in early endosomes. When the endosome has matured into a late endosome/MVB and fuses with a lysosome, the ... returns from the early endosome to the cell surface, both directly and via recycling endosomes. Transport from late endosomes ...
Gene Ontology Term: late endosome membrane. GO ID. GO:0031902 Aspect. Cellular Component. Description. The lipid bilayer ... surrounding a late endosome.. View GO Annotations in other species in AmiGO ...
... Gunnar K. Gouras ... Gunnar K. Gouras, "Convergence of Synapses, Endosomes, and Prions in the Biology of Neurodegenerative Diseases," International ...
Within five minutes, most of the receptors had transferred to the ASRT domains of endosomes. But when the team inhibited the ... But recent evidence shows that GPCRs can signal from the cell membrane and from endosomes, suggesting that the move could alter ... But GPCRs that possess these sequences home in on tubular sections of the endosome that carry actin/sorting nexin/retromer ( ... In contrast, other types of receptors that also travel to the endosomes after they bind their ligands, such as nutrient ...
Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
... Eathiraj S., Mishra A., Prekeris R., Lambright ... and that a critical determinant of Rab11 binding in vitro is necessary for FIP3 recruitment to recycling endosomes during ...
Endosomes and Lysosomes: A Dynamic Relationship, 1993, Buch, 978-1-55938-362-2. Bücher schnell und portofrei ... Our understanding of endosomes and lysosomes has undergone a molecular revolution over the last decade. Hence, we now know much ... In fact, endosomes may well not be discrete entities but rather continuously changing and evolving in their molecular ... Because of this vast increase in knowledge of molecules, we have realized that endosomes in particular are very ephemeral ...
Cripto Localizes Nodal at the Limiting Membrane of Early Endosomes. By Marie-Hélène Blanchet, J. Ann Le Good, Viola Oorschot, ... Cripto Localizes Nodal at the Limiting Membrane of Early Endosomes. By Marie-Hélène Blanchet, J. Ann Le Good, Viola Oorschot, ... Cripto Localizes Nodal at the Limiting Membrane of Early Endosomes Message Subject. (Your Name) has forwarded a page to you ... Thus, we propose that Cripto stimulates Nodal activity by localizing it at the interface of endosomes with cytoplasmic ...
Some endocytosed material passes through endosomes on its way to lysosomes. Endosomes are in part responsible for the sorting ... In biology, an endosome is a membrane-bound compartment inside cells, roughly 300-400 nm in diameter when fully mature[1]. Many ... In the acidic endosome, the iron is released from transferrin and then the iron-free transferrin (still bound the transferrin ... Ganley et.al, Rab9 GTPase Regulates Late Endosome Size and Requires Effector Interaction for Its Stability, Molecular Biology ...
Thus, MVEs operate in the endosome-to-lysosome portion of the pathway. In yeast cells, where MVE formation has been extensively ... multivesicular endosome. In part, the internalization and targeting of membrane proteins to the MVE involves ubiquitin, a ... Multivesicular endosomes (MVEs) are complex intracellular organelles that function in endocytosis. A major function of the ... Multivesicular endosomes (MVEs) are complex intracellular organelles that function in endocytosis. A major function of the ...
Endosome-Mediated Signaling in Plants. 07/01/2007. Endosome-Mediated Signaling in Plants. ... Endosomes were once thought to function solely in the inactivation of receptors and the down-regulation of cell signaling. Work ... "These findings will influence our thinking of the evolutionary origins of endosomes and hopefully help us to understand why ... Niko Geldner, Joanne Chory and colleagues (The Salk Institute and HHMI) demonstrate that endosomes can function as signaling ...
Additional EYFP-Endosome Images with the YFP HYQ Filter Combination. HeLa Human Cervical Carcinoma Cellular Endosomes. ... Enhanced Yellow Fluorescent Protein (EYFP) Endosome Localization. In eukaryotic cells, endosomes constitute a large network of ... Canine Kidney Cellular Endosomes. Fluorescence emission intensity from a culture of canine kidney (Madin-Darby; MDCK line) ... an enzyme that is localized in early endosomes, recycling endosomes, and multivesicular bodies. Upon transcription and ...
Endosomes Is the Subject Area "Endosomes" applicable to this article? Yes. No. ... Correction: Neuron Specific Rab4 Effector GRASP-1 Coordinates Membrane Specialization and Maturation of Recycling Endosomes ...
Signaling endosome-mediated events in cell bodies and dendrites. On reaching cell bodies, Trk-harboring endosomes stimulate ... Signaling endosome-mediated events in cell bodies and dendrites. *Defects in signaling endosomes in neurodevelopmental ... is recruited to Trk endosomes, and prevents the fusion of endosomes with lysosomes. [PMC free article] [PubMed] ... with Trk-containing endosomes transitioning from early to late endosomes. Alternatively, it is possible that several distinct ...
APOE [early endosome] (Homo sapiens) * CR:atREs [early endosome] (Homo sapiens) * CR [early endosome] (Homo sapiens) * APOE [ ... APOE [early endosome] (Homo sapiens) * CR:atREs [early endosome] (Homo sapiens) * CR [early endosome] (Homo sapiens) * APOE [ ... APOE [early endosome] (Homo sapiens) * CR:atREs [early endosome] (Homo sapiens) * CR [early endosome] (Homo sapiens) * APOE [ ... APOE [early endosome] (Homo sapiens) * CR:atREs [early endosome] (Homo sapiens) * CR [early endosome] (Homo sapiens) * APOE [ ...
TLR3 [endosome membrane] (Homo sapiens) * viral dsRNA :TLR3 [endosome membrane] (Homo sapiens) * TLR3 [endosome membrane] (Homo ... SARM:TICAM1:viral dsRNA:TLR3 [endosome membrane] (Homo sapiens) * viral dsRNA:TLR3:TICAM1 [endosome membrane] (Homo sapiens) * ... viral dsRNA:TLR3:TRIF:TRAF6 [endosome membrane] (Homo sapiens) * viral dsRNA:TLR3:TICAM1 [endosome membrane] (Homo sapiens) * ... viral dsRNA:TLR3:TRIF:TRAF6 [endosome membrane] (Homo sapiens) * viral dsRNA:TLR3:TICAM1 [endosome membrane] (Homo sapiens) * ...
A novel class of clathrin-coated vesicles budding from endosomes. J. Cell Biol. 132:21-33. doi:10.1083/jcb.132.1.21. ... Unconventional secretion of FABP4 by endosomes and secretory lysosomes. View ORCID ProfileJulien Villeneuve, View ORCID Profile ... Unconventional secretion of FABP4 by endosomes and secretory lysosomes. Julien Villeneuve, Laia Bassaganyas, Sebastien Lepreux ... Dynamin-dependent transferrin receptor recycling by endosome-derived clathrin-coated vesicles. Mol. Biol. Cell. 13:169-182. doi ...
... calcium channel required for neurotransmitter release also regulates the fusion of neuronal lysosomes with endosomes and ...
In pIIb, Delta passes through the recycling endosome which is marked by Rab 11. In pIIa, however, the recycling endosome does ... Asymmetric Rab 11 endosomes regulate delta recycling and specify cell fate in the Drosophila nervous system Cell. 2005 Sep 9; ... Using a mammalian cell culture system, we demonstrate that recycling endosomes are essential for Delta activity. Our results ... a Rab 11 binding partner that is essential for recycling endosome formation. ...
  • Molecules are also transported to endosomes from the trans-Golgi network and either continue to lysosomes or recycle back to the Golgi. (wikipedia.org)
  • Here, we show that mutations in class C and D Vps components, which mediate Golgi-to-endosome vesicle transport, impair nuclear translocation of Gln3, NCR gene activation, and growth in poor nitrogen sources. (pnas.org)
  • Moreover, class D vps mutants exhibit similar defects, implicating Golgi-to-endosome trafficking as a critical event for Gln3 regulation. (pnas.org)
  • Schekman, "Amyloid precursor protein (APP) traffics from the cell surface via endosomes for amyloid [beta] (A[beta]) production in the trans-Golgi network," Proceedings of the National Academy of Sciences of the United States of America, vol. (thefreedictionary.com)
  • Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes. (thefreedictionary.com)
  • In plant cells, secretory and endocytic routes intersect at the trans-Golgi network ( TGN )/early endosome ( EE ), where cargos are further sorted correctly and in a timely manner. (plantphysiol.org)
  • Stabilin-1 localizes to endosomes and the trans-Golgi network in human macrophages and interacts with GGA adaptors. (diva-portal.org)
  • X‐chromosome‐encoded σ1B is one out of three isogenes (termed A-C) for the tiny σ subunit of AP‐1 (comprising γ1, β1, μ1 and σ1 adaptins) localized to the trans‐Golgi network (TGN) and endosomes. (embopress.org)
  • Previous work showed that the multisubunit complex GARP (Golgi-Associated Retrograde Protein), composed of Ang2, Vps52, Vps53 and Vps54 subunits, functions as a tethering factor in retrograde transport from endosomes to the trans-Golgi network (TGN). (nih.gov)
  • Humans have two closely related Arl5 paralogues (Arl5a and Arl5b), and both Arl5a and Arl5b localize to the trans-Golgi with Arl5b being involved in retrograde traffic from endosomes to the Golgi apparatus. (biologists.org)
  • These phenotypes are consistent with a role in endosome-to-Golgi traffic, but are less severe than loss of GARP itself. (biologists.org)
  • They are originated from early endosomes and receive acid hydrolases from the Golgi complex. (uvigo.es)
  • Fluorescence emission intensity from a culture of human cervical adenocarcinoma ( HeLa line) epithelial cells that were transfected with a pEYFP-Endosome plasmid subcellular localization vector. (microscopyu.com)
  • Fluorescence emission intensity from a culture of rat thoracic aorta medial layer ( A-10 line) myoblast cells that were transfected with a pEYFP-Endosome plasmid subcellular localization vector. (microscopyu.com)
  • In contrast, if antigens were delivered to early endosomes through CD40 or CD11c, BDCA1 + DCs were as efficient at cross presentation as BDCA3 + DCs. (rupress.org)
  • In a paper that will be published online in advance of its July 1st publication date, Drs. Niko Geldner, Joanne Chory and colleagues (The Salk Institute and HHMI) demonstrate that endosomes can function as signaling platforms in plants, as well as in animals. (cshlpress.com)
  • Phosphotidyl inositol phosphates (PIPs), one of the most important lipid signaling molecules, is found to differ as the endosomes mature from early to late. (wikipedia.org)
  • Drs. Geldner, Chory and collaborators now extend the range of endosome-mediated signaling into the plant kingdom. (cshlpress.com)
  • In this review, we summarize the molecular mechanisms underlying this endosome-mediated signaling, focusing on the instructive role of neurotrophin signaling itself in directing its own trafficking. (pubmedcentralcanada.ca)
  • In this review, we discuss the regulatory role of neurotrophin-mediated signaling itself in directing the formation and retrograde transport of neurotrophin-harboring signaling endosomes. (pubmedcentralcanada.ca)
  • Here, we report that the recycling endosome-resident palmitoyl acyltransferase DHHC2 interacts with and palmitoylates AKAP79/150 to regulate these plasticity signaling mechanisms. (jneurosci.org)
  • Thus, we conclude that DHHC2-AKAP79/150 signaling is an essential regulator of dendritic recycling endosome exocytosis that controls both structural and functional plasticity at excitatory synapses. (jneurosci.org)
  • 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)
  • These data suggest that targeting of Shoc2 to late endosomes may facilitate EGFR-induced ERK activation under physiological conditions of cell stimulation by EGF, and therefore, may be involved in the spatiotemporal regulation of signaling through the RAS-RAF module. (uky.edu)
  • We expect that the unravelling of the complex relationship between early endosomes, mitochondria, iron and signaling and cancer progression will provide new tools for cancer therapy and diagnosis. (grantome.com)
  • In summary, to advance our basic understanding of breast cancer cell biology on a subcellular level, we will investigate the role of the morphology and function of early endosomes and their interaction with mitochondria on the regulation of iron homeostasis and receptor- mediated signaling pathways in 3D breast tumor systems. (grantome.com)
  • Early endosomes play a crucial role in the transport of metabolic nutrients, such as iron, as well as in receptor signaling via epithelial growth factor receptor. (grantome.com)
  • It remains unclear whether nanoparticles with certain properties could impact the physiological functions of endosomes. (biomedcentral.com)