SNARE

Definition: SNAREs are compartmentally specific, cytoplasmically oriented integral membrane proteins involved in the fusion of membranes and the transport of intracellular proteins. Recognition of vesicles and target membranes is mediated by vesicle SNAREs (v-SNAREs) and target SNAREs (t-SNAREs).

Synaptobrevins or VAMPs, syntaxins (MIM.186590), and the 25-kD synaptosomal-associated protein SNAP25 (MIM.600322) are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane called the SNARE complex(SNAP receptor).

A major problem of intracellular membrane traffic concerns the way in which transport vesicles find and fuse with their target organelles. SNARE proteins are involved in this fusion, and their mutual recognition could provide the necessary specificity.

Since the discovery of SNARE proteins in the late 1980s, SNAREs have been recognized as key components of protein complexes that drive membrane fusion.

Despite considerable sequence divergence among SNARE proteins, their mechanism seems to be conserved and is adaptable for fusion reactions as diverse as those involved in cell growth, membrane repair, cytokinesis and synaptic transmission.

Components

 vesicle SNAREs

• synaptotagmin
• synaptophysin
• synaptobrevin-1
• synaptobrevin-2

 target SNAREs

• syntaxin 1A
• SNAP25 (SNAP-25 A/B)

To fuse transport vesicles with target membranes (vesicular trafficking), proteins of the SNARE complex must be located on both the vesicle and the target membrane.

The specificity of vesicular transport is thought to be determined by correct pairing of vesicle-associated SNAREs (v-SNAREs) with those on the target membrane (t-SNAREs).

This complex then recruits soluble NSF attachment proteins (SNAPs) and N-ethylmaleimide-sensitive factor (NSF) (MIM.601633) to form a 20S fusion (or SNARE) complex.

References

 Jahn R, Scheller RH. SNAREs—engines for membrane fusion. Nat Rev Mol Cell Biol. 2006 Sep;7(9):631-43. PMID: 16912714

 Hong W. Cytotoxic T lymphocyte exocytosis: bring on the SNAREs! Trends Cell Biol. 2005 Dec;15(12):644-50. PMID: 16260137

 Breidenbach MA, Brunger AT. New insights into clostridial neurotoxin-SNARE interactions. Trends Mol Med. 2005 Aug;11(8):377-81. PMID: 16006188

 Toonen RF, Verhage M. Vesicle trafficking: pleasure and pain from SM genes. Trends Cell Biol. 2003 Apr;13(4):177-86. PMID: 12667755

 Rizo J, Sudhof TC. Snares and Munc18 in synaptic vesicle fusion. Nat Rev Neurosci. 2002 Aug;3(8):641-53. PMID: 12154365

 Chen YA, Scheller RH. SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol. 2001 Feb;2(2):98-106. PMID: 11252968

 Tooze SA, Martens GJ, Huttner WB. Secretory granule biogenesis: rafting to the SNARE. Trends Cell Biol. 2001 Mar;11(3):116-22. PMID: 11306272

 Pelham HR. SNAREs and the specificity of membrane fusion. Trends Cell Biol. 2001 Mar;11(3):99-101. PMID: 11306253