tSNARE

tSNARE refers to a class of SNARE proteins located on target membranes that mediate vesicle fusion by forming a stable trans-SNARE complex with v-SNAREs on transport vesicles. In most eukaryotic trafficking pathways, fusion requires complementary SNAREs: t-SNAREs on the target membrane and v-SNAREs on the vesicle; the association into a four-helix SNARE bundle brings the two membranes into close proximity to drive fusion. The most studied t-SNAREs are syntaxins (typical Q-SNAREs) and SNAP-25 or SNAP-23, which pair with vesicle-associated SNAREs such as synaptobrevin/VAMP. Neuronal exocytosis commonly uses syntaxin-1, SNAP-25, and VAMP2, whereas other secretory routes use different syntaxins and SNAPs.

Function and regulation: The SNARE complex formation is regulated by SM proteins (e.g., Munc18 family) and Rab GTPases that coordinate tethering and specificity. After fusion occurs, NSF and alpha-SNAP disassemble SNARE complexes for recycling. Calcium signals in neurons are sensed by synaptotagmin, triggering rapid fusion through a Ca2+-dependent acceleration of SNARE zippering.

Clinical and technical relevance: Disruption of tSNARE function blocks exocytosis; botulinum and tetanus toxins cleave t-SNAREs (and one v-SNARE) to inhibit neurotransmitter release, a basis for their clinical effects. Alterations in SNARE expression or function have been linked to neurodegenerative and metabolic disorders, and SNARE machinery is a target in research on secretion and membrane trafficking.