Disease relevance of Clathrin-Coated Vesicles

• Transport of the membrane glycoprotein of vesicular stomatitis virus to the cell surface in two stages by clathrin-coated vesicles [1].
• Whole cell lysates and membranes derived from rat brain, neuroblastoma cells and bovine brain clathrin-coated vesicles express the mature 150-165 kDa and 130 kDa unglycosylated forms of CFTR [2].

High impact information on Clathrin-Coated Vesicles

• This endocytic process requires AP180 (or a homolog), which promotes the assembly and restricts the size of clathrin-coated vesicles [3].
• We now report that ARF is also required for the binding of the AP-1 adaptor protein of clathrin-coated vesicles to Golgi membranes [4].
• Cbl rapidly recruits CIN85 (Cbl-interacting protein of 85K; ref. 6) and endophilins (regulatory components of clathrin-coated vesicles) to form a complex with activated EGF receptors, thus controlling receptor internalization [5].
• Epsin is associated with clathrin coats in situ, can be co-precipitated with AP-2 and Eps15 from brain extracts, but does not co-purify with clathrin coat components in a clathrin-coated vesicle fraction [6].
• Furthermore, we have reconstituted these effects in a cell-free system and established that Rho and Rac can regulate clathrin-coated vesicle formation [7].

Biological context of Clathrin-Coated Vesicles

• We have examined the roles of Hsc70 and auxilin in the uncoating of clathrin-coated vesicles (CCVs) during neuronal endocytosis [8].
• Hydrolysis of GTP by dynamin is essential for budding clathrin-coated vesicles from the plasma membrane [9].
• Dopamine acutely stimulates Na+/H+ exchanger (NHE3) endocytosis via clathrin-coated vesicles: dependence on protein kinase A-mediated NHE3 phosphorylation [10].
• Amantadine, which blocks the budding of clathrin-coated vesicles, inhibited phagocytosis from 13.8+/-0.8 to 5.7+/-0.6 (p<0.01) [11].
• Here we demonstrate that aftiphilin has a second, atypical clathrin binding site, YQW, that colocalizes with AP-1 by immunofluorescence, and that is enriched in clathrin-coated vesicles (CCVs), confirming that it is a bona fide component of the CCV machinery [12].

Anatomical context of Clathrin-Coated Vesicles

• Although clathrin-coated vesicles mediate the export of mannose 6-phosphate receptors from the TGN, nothing is known about the transport vesicles used to carry these receptors back to the TGN [13].
• Hip1R, an F-actin-binding protein that associates with clathrin-coated vesicles, may physically link endocytic vesicles to actin filaments [14].
• We and others recently have demonstrated adenosine triphosphate-dependent acidification in a variety of prelysosomal organelles isolated from liver including clathrin-coated vesicles, multivesicular bodies, and Golgi [15].
• Immunoelectron microscopy suggests that whereas transmembrane CD4 is endocytosed via clathrin-coated vesicles, CD4DAF enters cells by an alternative pathway involving non-coated microinvaginations of the plasma membrane [16].
• This was associated with impaired incorporation of the cation-independent mannose 6-phosphate receptor into clathrin-coated vesicles at the TGN, partial redistribution of the receptor to endosomes, and missorting of cathepsin D. The morphology of the TGN was also altered [17].

Associations of Clathrin-Coated Vesicles with chemical compounds

• In the past year, examples of phosphoinositide effectors include regulators of small GTPases in coat assembly, dynamin in clathrin coated vesicle formation and FYVE finger proteins in endocytic membrane traffic [18].
• RNAi-mediated CPG2 knockdown increases the number of postsynaptic clathrin-coated vesicles, some of which traffic NMDA receptors, disrupts the constitutive internalization of glutamate receptors, and inhibits the activity-induced internalization of synaptic AMPA receptors [19].
• Hub expression blocked lysosomal delivery of chimeric molecules containing either the tyrosine-based sorting signal of H2M or the dileucine-based sorting signal of CD3gamma, confirming a role for clathrin-coated vesicles (CCVs) in recognizing these signals and sorting them to the endocytic pathway [20].
• In the principal cell vesicle recycling is induced by a specific hormone, vasopressin, and involves clathrin-coated vesicles in the endocytotic step of the cycle [21].
• Mannose 6-phosphate receptors regulate the formation of clathrin-coated vesicles in the TGN [22].

Gene context of Clathrin-Coated Vesicles

• CHC17 forms the ubiquitous clathrin-coated vesicles that mediate membrane traffic [23].
• The distinctive granular cytoplasmic staining pattern for ALK was likely to be due to binding of the fusion protein to clathrin-coated vesicles [24].
• A significant amount of Clint copurifies with rat liver clathrin-coated vesicles [25].
• Moreover, HIP1 binding to CLC is necessary for HIP1 targeting to clathrin-coated pits and clathrin-coated vesicles [26].
• We propose that NLRR-3 potentiates Ras-MAPK signaling by facilitating internalization of EGF in clathrin-coated vesicles [27].

Analytical, diagnostic and therapeutic context of Clathrin-Coated Vesicles

• Western blot analysis revealed clathrin-coated vesicles extracted with detergent retained ARF [28].
• DNA entrapped in liposomes containing lactosylceramide in the bilayers is found to be associated with clathrin-coated vesicles isolated from the rat livers after intravenous injection of these liposomes [29].
• The kinase copurifies in gel filtration, adsorption on hydroxylapatite, and ion exchange chromatography with the HAI assembly proteins which are part of the coat of Golgi-derived clathrin-coated vesicles [30].
• The activator, which requires detergent (polyoxyethylene 9-lauryl ether) for release from clathrin-coated vesicles, is heat-stable, trypsin-sensitive, and has an apparent molecular mass of about 6 kDa as determined by high performance liquid chromatography [31].
• Electron microscopy and immunogold studies also demonstrate that the surface of clathrin-coated vesicles are also immunolabelled for both alpha-adaptin and PSA-NCAM, the highly sialylated isoform of NCAM [32].

References