syt

Syt, short for synaptotagmin, refers to a family of membrane-embedded proteins that act as calcium sensors to trigger regulated exocytosis in neurons and other secretory cells. These proteins are typically anchored in vesicle membranes and respond to elevations in intracellular calcium by promoting fusion of the vesicle with the plasma membrane, releasing neurotransmitters or hormones.

Most synaptotagmins contain a single transmembrane helix near the N-terminus and two cytosolic C2 domains (C2A and C2B) that bind calcium and phospholipids. The C2 domains undergo conformational changes upon Ca2+ binding that enable interactions with SNARE proteins and acidic phospholipids, thereby accelerating SNARE-mediated membrane fusion.

The SYT gene family includes multiple isoforms (for example SYT1, SYT2, SYT7, and others) with tissue-specific expression patterns. SYT1 is the best characterized and is thought to serve as the principal sensor for fast, synchronous neurotransmitter release in many central synapses. Other isoforms contribute to slower, asynchronous release, peptide and hormone secretion, or lysosomal exocytosis. Genetic disruption in model organisms or humans can impair neurotransmission and cause developmental or neurological phenotypes; mutations in SYT1 have been linked to neurodevelopmental disorders.

Discovery and significance: Synaptotagmins were identified in the 1990s through work on the molecular machinery of exocytosis and SNAREs. They are central to current models of how calcium triggers rapid vesicle fusion and transmitter release.