SNARE proteins are involved in the fusion of vesicles with their target membranes. Synaptosomal-associated protein 25 (SNAP-25) regulates Kv2.1 voltage-dependent K(+) channels in pancreatic beta cells []. It may also play a role in neurotansmiiter release form the synapse. It is a component of the SNARE core complex, which also includes VAMP2 and STX1A [, ]. In some fish species (goldfish, zebrafish) there are two homologues known as SNAP-25A and SNAP-25B.
Doc2a (double C2-like domain-containing protein alpha) and Doc2b (double C2-like domain-containing protein beta) are members of the double C2 domain protein family. Doc2a is expressed in neuronal cells and has been implicated in Ca2+-dependent neurotransmitter release [, ]. Doc2a exhibits Ca2+-dependent phospholipid-binding activity through its C2A domain, which is thought to be important for the regulation of Ca2+-dependent exocytosis. The C2B domain is required for binding of syntaxin-1a/synaptosome-associated protein of 25kDa (SNAP-25) heterodimer []. Doc2a is also expressed in pancreatic islets, and has been implicated together with Doc2b in the synergistic regulation of glucose-stimulated insulin secretion [].Doc2b contains two calcium and phospholipid binding domains in its C terminus []. It interacts with the SNARE (soluble N-ethylmaleimide-sensitive factor attached protein receptor) complex composed of SNAP25, STX1A and VAMP2. Doc2b regulates SNARE-dependent fusion of vesicles with membranes in a calcium-dependent manner. It is involved in calcium-dependent spontaneous release of neurotransmitter, with a function analogous to synaptotagmin-1, but with a higher Ca2+ sensitivity []. Doc2b is a positive SNARE regulator for glucose transporter GLUT4 vesicle fusion and mediates insulin-stimulated glucose transport in adipocytes []. It is involved in both insulin-stimulated glucose uptake in adipocytes and glucose-stimulated insulin secretion in pancreatic cells, as well as insulin responsiveness in skeletal muscle [, ].
