Vesicle-associated membrane protein 2 (VAMP2, also known as Synaptobrevin-2) belongs to the VAMP family, which is a group of small, integral membrane proteins of synaptic vesicles that is mostly involved in vesicle fusion. Neurotransmitter release involves the assembly of a heterotrimeric SNARE complex composed of SNAP25, VAMP2 and syntaxin 1 []. VAMP2 plays a specific role in the insulin-dependent recruitment of GLUT4 from its intracellular storage compartment to the cell surface [].
This entry includes vesicle-associated membrane proteins VAMP1/synaptobrevin-1, VAMP2/synaptobrevin-2, VAMP3/synaptobrevin-3 and VAMP8/endobrevin.VAMPs are a group of small, integral membrane proteins of synaptic vesicles that is mostly involved in vesicle fusion. The heterotrimeric SNARE complex isformed by syntaxin 1, synaptosomal-associated protein 25kDa (SNAP25), and vesicle-associated membrane protein (VAMP)/synaptobrevin []. VAMP1 plays an essential, non-redundant role in Ca2+-triggered vesicle exocytosis at the mouse neuromuscular junction []. VAMP2 is extensively expressed in the central nervous system []. Neurotransmitter release involves the assembly of a heterotrimeric SNARE complex composed of SNAP25, VAMP2 and syntaxin 1 []. VAMP8 may be involved in regulated exocytosis of the exocrine system [, ].
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.
Septin 8 (SEPT8) belongs to the septin family. It suppresses the interaction between VAMP2 (vesicle-associated membrane protein 2) and synaptophysin through binding to VAMP2. It also forms a complex with syntaxin1A and may participate in the process of the SNARE complex formation and subsequent neurotransmitter release [].Septins were first discovered in budding yeast as a major component of bud neck filaments during cell septation [, ]. Later, its homologues were identified in nearly all eukaryotes, including humans. They are all GTP-binding proteins that are involved in diverse cellular functions, including cell cycle progression, vesicle trafficking, cytokinesis, cell migration, membrane dynamics, and chromosome segregation [, ]. Similar to cytoskeleton components such as actins and tubulins, they can assemble into filaments and bundles. However, unlike actin filaments and microtubules, septin filaments are not polar, similarly to intermediate filaments []. The number of septin genes per organism is variable: S. cerevisiae has seven and humans have 13 (SEPT1-12 and SEPT14; SEPT13 is a pseudogene now called SEPT7P2) []. All septins can form heteromeric complexes, which associate to form higher-order structures, including filaments, rings and cage-like formations [, ].
Clathrin is a triskelion-shaped cytoplasmic protein that polymerises into a polyhedral lattice on intracellular membranes to form protein-coated membrane vesicles. Lattice formation induces the sorting of membrane proteins during endocytosis and organelle biogenesis by interacting with membrane-associated adaptor molecules. Clathrin functions as a trimer, and these trimers, or triskelions, are comprised of three legs joined by a central vertex. Each leg consists of one heavy chain and one light chain. The clathrin heavy-chain contains a 145-residue repeat that is present in seven copies [, ]. The clathrin heavy-chain repeat (CHCR) is also found in nonclathrin proteins such as Pep3, Pep5, Vam6, Vps41, and Vps8 from Saccharomyces cerevisiae and their orthologs from other eukaryotes [, , , ]. These proteins, like clathrins, are involved in vacuolar maintenance and protein sorting. The CHCR repeats in these proteins could mediate protein-protein interactions, or possibly represent clathrin-binding domains, or perform clathrin-like functions. CHCR repeats in the clathrin heavy chain, Saccharomyces cerevisiae Vamp2 and human Vamp6 have been implicated in homooligomerization, suggesting that this may be the primary function of this repeat.The CHCR repeat folds into an elongated right-handed superhelix coil of short α-helices []. Individual 'helix-turn-helix-loop' or helix hairpin units comprise the canonical repeat and stack along the superhelix axis to form a single extended domain. The canonical hairpin repeat of the clathrin superhelix resembles a tetratrico peptide repeat (TPR), but is shorter and lacks the characteristic spacing of the hydrophobic residues in TPRs.
