TSNAREs

tSNAREs, or target SNAREs, are a class of SNARE proteins located on the membranes of target organelles. They participate in the final steps of vesicular transport by forming a SNARE complex with vSNAREs on the transport vesicle, driving membrane fusion. In most pathways the core complex comprises three Q-SNARE motifs contributed by the target membrane and one R-SNARE motif contributed by the vesicle. The three Q-SNAREs are typically provided by a syntaxin (Qa) and the SNAP-25 family (providing Qb and Qc), together with a vesicular VAMP/synaptobrevin acting as the R-SNARE. The assembled four-helix bundle brings the opposing membranes into close proximity, promoting lipid mixing and fusion.

Formation and regulation: The interaction forms a trans-SNARE complex across the vesicle-target interface, which then zippers from the N- to C- terminus to catalyze fusion. After fusion, the cis-SNARE complex is disassembled by the ATPase NSF in cooperation with α-SNAP to recycle SNAREs for another round of trafficking. SNARE assembly is modulated by regulatory proteins, including SM (Sec1/Munc18) proteins, complexins, and synaptotagmins in neurons.

Distribution and roles: tSNAREs function in a wide range of trafficking steps, including neurotransmitter release at synapses, hormone secretion, and intracellular trafficking between endosomes, Golgi, and plasma membrane. Neuronal tSNAREs such as syntaxin-1, syntaxin-4, and SNAP-25 are well studied; non-neuronal tSNAREs contribute to essential secretory and endocytic processes.

Clinical and research relevance: Proper tSNARE function is essential for efficient vesicle fusion and cellular homeostasis; defects can disrupt trafficking and are investigated in the context of neurological and metabolic disorders.