VAMP-2 (also known as synaptobrevin-2) is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein superfamily. The family includes 36 members in humans and is characterized by the SNARE motif, an evolutionary conserved stretch of 60–70 amino acids that are arranged in heptad repeats^1,2.

SNARE proteins are involved in exocytosis and intracellular vesicle trafficking and are essential for cell growth, hormone secretion and neurotransmission, processes that require rapid, targeted, and regulated membrane fusion^1,2.

SNAREs can be roughly divided into vesicular (v-SNAREs) and target (t-SNAREs) based on their distribution on the transport vesicle or target membrane respectively. Thus, assembly of cognate v-/t-SNAREs between two opposing membranes generates trans-SNARE complexes, which bring the lipid bilayers in close proximity and drive membrane fusion.

VAMP-2, like most SNAREs, is a type IV membrane protein with a relatively large N-terminus containing the SNARE motif located on the cytoplasmic side and a transmembrane domain located close to the C-terminus that functions as an anchor^1,2.

VAMP-2 has been extensively studied for its role on neuronal and neuroendocrine cell exocytosis where it functions as the vesicle membrane protein v-SNARE, which together with the plama membrane t-SNARE protein Syntaxin 1 and the membrane-associated SNAP-25 (synaptosome-associated protein 25 kDa), forms a trimeric, four-helical complex, which drives fusion of the two opposing bilayers^1,2.

VAMP-2 is the target of the tetanus neurotoxin (TeNT) and of several botulinum neurotoxin (BoNT) types: type B, D, F, and G. The neurotoxins cause specific proteolytic degradation of the VAMP-2 protein, which in turn causes SNARE complex disruption and inhibition of neurotransmitter release³.