Disease relevance of Vamp3

• Consistently, tetanus toxin had no effect on secretion from permeabilized mouse VAMP-3(-/-) platelets or human platelets, despite cleavage of VAMP-2 and/or -3 [1].
• The VAMP3 null mice had typical growth rate and weight gain, with normal maintenance of fasting serum glucose and insulin levels [2].
• Cellubrevin alterations and Mycobacterium tuberculosis phagosome maturation arrest [3].

High impact information on Vamp3

• We find that synaptobrevin II and cellubrevin differentially control the pool of readily releasable vesicles and show that the v-SNARE's amino terminus regulates the vesicle's primed state [4].
• We conclude that a proportion of GLUT-4 is found in recycling endosomes in nonstimulated adipocytes together with cellubrevin and the transferrin receptor [5].
• VAMP-2 and cellubrevin were: (a) the most abundant isoforms in adipocytes, (b) detectable in all insulin responsive tissues, (c) translocated to the cell surface in response to insulin, and (d) found in immunoadsorbed GLUT-4 vesicles [5].
• Using cell fractionation in combination with immunoisolation, these vesicles are enriched in a light fraction and shown to contain the cellular vSNARE cellubrevin and the ubiquitous SCAMPs in epithelial cells and synaptophysin in neuroendocrine or cDNA-transfected nonneuroendocrine cells and neuroendocrine tissues [6].
• Tetanus neurotoxin-mediated cleavage of cellubrevin impairs epithelial cell migration and integrin-dependent cell adhesion [7].

Biological context of Vamp3

• Here, we show that each of the vesicle-associated SNARE proteins (v-SNARE) of a chromaffin granule, synaptobrevin II or cellubrevin, is sufficient to support Ca(2+)-dependent exocytosis and to establish a pool of primed, readily releasable vesicles [4].
• In addition, other general membrane trafficking events including phagocytosis, pinocytosis, and transferrin receptor recycling were also found to be unaffected in the VAMP3 null mice [2].
• Rate and extent of phagocytosis in macrophages lacking vamp3 [8].
• These results suggest that Cb-dependent membrane trafficking participates in cell motility through the regulation of cell adhesion [7].
• Testicular proteins associated with the germ cell-marker, TEX101: involvement of cellubrevin in TEX101-trafficking to the cell surface during spermatogenesis [9].

Anatomical context of Vamp3

• In this work, we report that cellubrevin, a v-SNARE functioning in endosomal recycling and implicated in endosomal interactions with post-Golgi compartments, plays a role in phagosomal maturation and that it is altered on mycobacterial phagosomes [3].
• Cellubrevin status on phagosomes had consequences on phagosomal membrane and lumenal content trafficking, involving plasma membrane marker recycling and delivery of lysosomal enzymes [3].
• Cellubrevin was markedly induced during differentiation of 3T3-L1 fibroblasts into adipocytes, in parallel with GLUT4, and the development of insulin regulated traffic [10].
• The beta cell lines were also shown to express a second vesicle (v)-SNARE, cellubrevin [11].
• From these results we concluded that cellubrevin-dependent membrane trafficking is involved in TEX101-transport to the surface of male germ cells [9].

Associations of Vamp3 with chemical compounds

• Insulin stimulation of glucose uptake in isolated primary adipocytes was essentially the same for the wild-type and VAMP3 null mice [2].
• Both mycobacterial phagosomes, which undergo maturation arrest, and model phagosomes containing latex beads, which follow the normal pathway of maturation into phagolysosomes, acquired cellubrevin [3].

Other interactions of Vamp3

• Immuno-EM on intracellular vesicles from adipocytes revealed that VAMP-2 was colocalized with GLUT-4, whereas only partial colocalization was observed between GLUT-4 and cellubrevin [5].
• BoNT/B was shown by immunoblotting to cause extensive proteolysis of Cbr and Sbr resulting in a significant blockade of the insulin-stimulated translocation of GLUT4 to the plasmalemma [12].
• Botulinum neurotoxin B inhibits insulin-stimulated glucose uptake into 3T3-L1 adipocytes and cleaves cellubrevin unlike type A toxin which failed to proteolyze the SNAP-23 present [12].
• Levels of the v-SNARE protein cellubrevin and of the t-SNARE protein syntaxin 4 were increased in this process in parallel to GLUT4 [13].
• Regardless of the phagocytic receptor engaged or particle load, BMM lacking vamp3 exhibited no phagocytic defects when assayed after 1 h at 37 degrees C, and phagosome maturation was unimpaired as judged by acquisition of lamp-1 [8].

Analytical, diagnostic and therapeutic context of Vamp3

• We used bone marrow-derived macrophages (BMM) from wild type and vamp3 null mice to evaluate directly the requirement for this v-SNARE in phagocytosis of zymosan, IgG-beads, complement-opsonized particles, or latex microspheres [8].
• Immunohistochemistry using a cellubrevin-specific antibody indicated that the molecule is abundant on spermatocytes and early-stage spermatids, whereas negligible amounts are found in Sertoli cells, spermatogonia, spermatozoa, and late-stage spermatids [9].

References