VAMPs

VAMPs, or vesicle-associated membrane proteins, are a family of SNARE proteins that mediate vesicular fusion in eukaryotic cells. They are typically anchored in the membrane of transport vesicles via a single C-terminal transmembrane domain. The cytosolic region contains a SNARE motif that participates in complex formation with target membrane SNAREs (t-SNAREs), forming the SNARE complex that drives membrane fusion.

Members include VAMP1, VAMP2 (synaptobrevin I and II), VAMP3 (cellubrevin), VAMP4, VAMP7 (TI-VAMP), and VAMP8 (endobrevin). VAMP1 and VAMP2 are highly expressed in neurons and are central to the release of neurotransmitters at synapses. VAMP3 is widely expressed and supports constitutive exocytosis. VAMP4, VAMP7, and VAMP8 function in various endosomal and lysosomal fusion events and non-neuronal secretory pathways; VAMP7 in late endosome/lysosome fusion and secretory granule trafficking, and VAMP8 in endosome-to-lysosome traffic and mucosal secretory pathways.

The SNARE complex is formed with target membrane t-SNAREs such as syntaxin and SNAP-25, creating a four-helix bundle that brings membranes into close proximity to drive fusion. This process is tightly regulated by proteins including Munc18, complexins, and other accessory factors.

VAMPs are targets of neurotoxic clostridial botulinum and tetanus toxins, which cleave specific VAMP family members to block synaptic transmission. Dysfunction or altered expression of VAMPs has been implicated in studies of neurological and secretory pathophysiology, although precise contributions vary by isoform and tissue.

In summary, VAMPs are essential components of the cellular machinery that mediates vesicle fusion and cargo release across diverse cell types, with specialized roles in neural and secretory processes.