SNAREprotein

SNARE proteins are a family of membrane-associated proteins that mediate intracellular vesicle fusion in eukaryotic cells. The term SNARE stands for soluble NSF attachment protein receptor, reflecting their role in catalyzing membrane fusion and their interaction with the ATPase NSF during SNARE complex recycling. SNAREs assemble into a four-helix bundle that brings vesicle and target membranes into close proximity, triggering bilayer fusion.

SNAREs are typically classified into v-SNAREs (vesicle-associated) and t-SNAREs (target membrane-associated). Classic neuronal examples include synaptobrevin/VAMP on synaptic vesicles as a v-SNARE, while syntaxin-1 and SNAP-25 function as t-SNAREs. SNAP-25 is anchored to the plasma membrane by palmitoylation rather than a transmembrane domain, whereas syntaxin-1 and synaptobrevin have a single transmembrane helix that anchors them.

The SNARE motif, about 60–70 amino acids long, forms a coiled-coil region that drives complex formation. SNARE proteins are further categorized as Q-SNAREs or R-SNAREs based on the central layer residue in the SNARE motif, with glutamine (Q) or arginine (R) occupying the zero layer. Typical neuronal complexes involve two Q-SNAREs (syntaxin and SNAP-25) and one R-SNARE (synaptobrevin).

Fusion proceeds via the formation of a trans-SNARE complex across the vesicle and target membranes, which zippers to a tight cis-SNARE complex and promotes lipid bilayer merger. After fusion, the complex is disassembled by the ATPase NSF and the adaptor α-SNAP, allowing SNAREs to be reused.

SNAREs function in numerous trafficking steps, including neurotransmitter release, ER-Golgi transport, and endosome-lysosome fusion. They are targets of bacterial neurotoxins, such as botulinum and tetanus toxins, which cleave SNARE proteins and block neurotransmitter release. Dysfunction or altered expression of SNAREs has been implicated in various neurological and secretory disorders.