Syntaxin

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Molecular machinery driving exocytosis in neuromediator release. The core SNARE complex is formed by four

α

-helices contributed by synaptobrevin, syntaxin and SNAP-25, synaptotagmin serves as a

C a 2 +

sensor and regulates intimately the SNARE zipping

Syntaxins (syntaxin isotypes 1-4) are membrane integrated Q-SNARE proteins participating in exocytosis. Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). The SNARE (H3) domain binds to both synaptobrevin and SNAP-25 forming the core SNARE complex. Formation of this incredibly stable SNARE core complex is believed to generate the free energy required to initiate fusion between the vesicle membrane and plasma membrane. The N-terminal Habc domain is formed by 3 $α$ -helices and when collapsed onto its own H3 helix forms an inactive "closed" syntaxin conformation. This closed conformation of syntaxin is believed to be stabilized by binding of nSec1 (Munc18), although more recent data suggests that nSec1 may bind to other conformations of syntaxin, as well. The "open" syntaxin conformation is the conformation that is competent to form into SNARE core complexes.

Syntaxins bind synaptotagmin in a calcium-dependent fashion and interact with voltage-gated calcium channels (VGCCs) via the C-terminal H3 domain. Direct syntaxin-VGCC interaction is a suitable molecular mechanism for proximity between the fusion machinery and the gates of $C a 2 +$ entry during depolarization of the presynaptic axonal boutons.

In vitro syntaxin per se is sufficient to drive spontaneous calcium independent fusion of synaptic vesicles containing v-SNAREs. More recent and somewhat controversial amperometric data suggest that the transmembrane domain of Syntaxin1A may form part of the fusion pore of exocytosis.