syntaxin

Syntaxin is a family of membrane-anchored proteins that act as Q-SNAREs essential for regulated membrane fusion in eukaryotic cells. Most syntaxins are single-pass transmembrane proteins with a cytosolic N-terminus, a central SNARE motif, and a C-terminal transmembrane domain.

In vesicular trafficking, syntaxins function as target-SNAREs that form a SNARE complex with vesicle-SNAREs such as synaptobrevin/VAMP and SNAP-25. The four-helix complex drives membrane fusion, enabling processes such as neurotransmitter release, hormone secretion, and general exocytosis.

Isoforms and distribution: In mammals, several syntaxin genes encode proteins with distinct tissue patterns. Syntaxin-1A and -1B predominate in neurons, mediating fast, calcium-triggered release. Syntaxin-4 is widespread at plasma membranes, while syntaxin-5 participates in ER–Golgi trafficking; other isoforms function in endosomal routes and other intracellular membranes.

Regulation and interactions: Syntaxins interact with Sec1/Munc18-like (SM) proteins, such as Munc18-1, which regulate their conformation and SNARE complex assembly. After fusion, SNARE complexes are disassembled by NSF and α-SNAP. Phosphorylation and other post-translational modifications can modulate syntaxin activity and SNARE pairing.

Clinical relevance: Changes in syntaxin expression or function have been linked to neurodevelopmental and metabolic disorders in research studies. Genetic variation in syntaxin genes has been associated with certain conditions, but the mechanisms are multifactorial and remain under investigation.