Disease relevance of CD63

• IMPLICATIONS: Our results indicate that the data obtained in studies of these three melanoma antigens may be pooled, and we propose that the molecule recognized by these reagents be classified as CD63 [1].
• Immunolabeling demonstrated that these compartments contained the late endosomal marker CD63, which was enriched on vesicles within these structures and incorporated into the envelope of budding virions [2].
• All of the carcinomas were ME491/CD63 positive [3].
• During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63 [4].
• Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages [4].

High impact information on CD63

• Although the lysosomal protein CD63 was mislocalized to the plasma membrane, perforin and granzymes were correctly localized to the lytic granules in AP-3-deficient CTLs [5].
• The AP-3 deficiency results in increased surface expression of the lysosomal membrane proteins CD63, lamp-1, and lamp-2, but not of nonlysosomal proteins [6].
• In these structures FasL colocalizes with both melanosomal (i.e., gp100) and lysosomal (i.e., CD63) antigens [7].
• We additionally show that melanosome-containing multivesicular bodies degranulate extracellularly and release FasL-bearing microvesicles, that coexpress both gp100 and CD63 and retain their functional activity in triggering Fas-dependent apoptosis of lymphoid cells [7].
• The levels and expression of the proteins CD63 and granulophysin in platelets from control and from a Hermansky-Pudlak syndrome subject (a condition characterized by dense granule and lysosomal deficiencies and the accumulation of ceroid-like material in reticuloendothelial cells) were examined [8].

Chemical compound and disease context of CD63

• Among genes found differentially expressed, the CD63 tetraspanin, not previously recognized in colon cancer progression, and the alpha3 integrin chain were both up-regulated in low metastatic E2 cells and were analyzed for their functional role using adhesion, migration, and invasion assays [9].
• In addition, neopterin (r = 0.37, r = 0.44), IL6 (r = 0.37, r = 0.60) and CD63 expression (r = 0.39, r = 0.45) correlated significantly with disease activity as measured by the Birmingham Vasculitis Activity Score and C reactive protein values, respectively [10].
• CONCLUSION : The current study suggests that serine protein kinase activity associated with CD63 may play a role in signaling by CD63 in melanoma cells [11].
• Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs [12].
• In this study, we determined that in HeLa and T cells, the MA mutant Gag proteins that are defective in plasma membrane targeting form virus particles in a CD63-positive compartment, defined as the late endosome or multivesicular body (MVB) [13].

Biological context of CD63

• These data indicate that CD63 serves as an adaptor protein that links its interaction partners to the endocytic machinery of the cell and suggest a previously uncharacterized protein-trafficking role for the tetraspanins [14].
• Immunofluorescence and biochemical experiments reveal that this redistribution occurs by enhanced endocytosis of H,K-ATPase beta-subunit complexed with CD63 [14].
• CD63 is a 53-Kd lysosomal membrane glycoprotein that has been identified as a platelet activation molecule [15].
• CD63 tetraspanin slows down cell migration and translocates to the endosomal-lysosomal-MIICs route after extracellular stimuli in human immature dendritic cells [16].
• Complexes of monoclonal antibody (Mab) FC-5.01-CD63 or Fab-5.01-CD63 were rapidly translocated "outside-in" and followed the endocytic pathway through early endosomes and lysosomes, reaching major histocompatibility complex (MHC) class II-enriched compartments (MIICs) in less than one hour [16].

Anatomical context of CD63

• The beta-subunit and CD63 also interact when they are coexpressed in COS-7 cells [14].
• We find that CD63 is present also in tubulovesicular elements, the intracellular compartments that contain the H,K-ATPase in unstimulated gastric parietal cells [14].
• One antibody, 2C6, was found to be specific for CD63, a membrane glycoprotein previously described in the lysosomes of platelets and other cell types [17].
• CD63 is a component of Weibel-Palade bodies of human endothelial cells [17].
• Our results indicate that CD63 colocalizes with vWF and P-selectin in the Weibel-Palade bodies of endothelial cells, and together with these adhesion proteins it could be rapidly expressed on the cell surface in areas of vascular injury and inflammation [17].

Associations of CD63 with chemical compounds

• ME491 melanoma-associated glycoprotein family: antigenic identity of ME491, NKI/C-3, neuroglandular antigen (NGA), and CD63 proteins [1].
• Enzymatic and immunochemical assays show a phosphatidylinositol 4-kinase in novel and specific complexes with proteins (CD63 and CD81) of the transmembrane 4 superfamily (TM4SF) and an integrin (alpha3beta1) [18].
• Strong, tyrosine-dependent interaction of the wild-type carboxyterminal tail of CD63 with the AP-3 adaptor subunit mu 3 was observed using a yeast two-hybrid system [19].
• Here we show that prototype complexes of CD9 or CD81 (TM4SF proteins) with alpha(3)beta(1) (an integrin) and complexes of CD63 (a TM4SF protein) with phosphatidylinositol 4-kinase (PtdIns 4-K) may indeed localize within lipid raft-like microdomains, as seen by three different criteria [20].
• CD63 co-immunoprecipitated with a lipid kinase which, on the basis of enzymatic properties(stimulated by nonionic detergents, inhibited by adenosine), is consistent with PI 4-kinase type II [21].
• Coexpression of CD63 enhanced tyrosine phosphorylation of ROMK1 [22].

Physical interactions of CD63

• Double labeling with a CD63-specific antibody demonstrated selective binding of BB1 to the granule matrix [23].
• An immunoassay was developed in which ME491 was absorbed to polystyrene beads in order to bind the melanoma-associated antigen present in serum [24].

Regulatory relationships of CD63

• CD9 was expressed on the plasma membrane of enterocytes in crypts and at the bases of the villi whereas CD63 demonstrated a unique granular appearance concentrated in the apical cytoplasm below the brush border [25].
• Redistribution of TI-VAMP in the ER of syntaxin-1-expressing cells was microtubule dependent and impaired the trafficking of CD63, a cargo of TI-VAMP-containing vesicles [26].
• The expression of CD63 in CML-CP platelets was induced by TPO treatment [27].
• These results suggest that CD63 regulates MT1-MMP by targeting to lysosomes [28].
• Furthermore, internalization of CD63 was completely blocked in cells expressing a syntenin-1 mutant lacking the first 100 amino acids [29].

Other interactions of CD63

• Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs [30].
• These included an integrin (alpha6beta1) and three different TM4SF proteins (CD9, CD63, and NAG-2) [31].
• Also, cross-linking experiments established that alpha 3 beta 1/CD81, alpha 3 beta 1/CD9, and alpha 3 beta 1/CD63 associations occur on the surface of intact cells and suggested that a critical interaction site is located within extracellular domains [32].
• Particularly in this latter quality CD63 clearly surpasses several other CD28-independent costimulatory pathways previously described [33].
• CONCLUSION: The rise in CD63 during VIT indicates a partial basophil degranulation with release of stored protein mediators, including IL-4 [34].

Analytical, diagnostic and therapeutic context of CD63

• Immunofluorescence studies indicated that anti-CD63 and anti-granulophysin antibodies recognized similar numbers of granules; coapplication of antibodies did not identify more granules than the individual antibodies [8].
• A competition immunoprecipitation experiment also confirms the identity of CD63, as defined by MAb RUU-SP 2.28, with the three melanoma antigens [1].
• The expression of CD11b, CD66b and CD63 on the neutrophil cell surface, as a reflection of activation, was analysed using flow cytometry [35].
• They were clearly identified by electron microscopy after isolation by differential ultracentrifugation or immunoisolation with CD63-coated latex beads [36].
• Cell surface expression of CD63 and alpha3 integrin was about 2-fold higher in E2 than in C5 cells and confocal microscopy showed that CD63 and alpha3 integrin colocalized evenly on C5 cells whereas they concentrated at elongated tips of the low-metastatic more substrate-adhesive E2 cells [9].

References