Synaptotagmin-1 (SYT1)

Synaptotagmin-1 is a synaptic vesicle integral membrane protein serving as the principal calcium sensor for fast, synchronous neurotransmitter release in the central nervous system[1][3][6][8]. It contains an N-terminal transmembrane domain and two cytoplasmic C2 domains (C2A and C2B) that bind Ca\(^{2+}\) and acidic phospholipids[3][5]. Upon Ca\(^{2+}\) influx during an action potential, synaptotagmin-1 interacts with the SNARE complex and phospholipids, triggering rapid synaptic vesicle fusion and neurotransmitter release[1][5][6]. It also acts as a molecular clamp, suppressing spontaneous and asynchronous release through oligomerization and interactions with complexin and SNARE proteins[2][5]. Mutations in SYT1 can impair synaptic function and are associated with some neuropsychiatric disorders[8]. While it is not currently the direct target of any approved therapeutic, it represents a mechanistic node essential for synaptic communication.

Other names

Synaptotagmin ISYT ISyt1p65

Calcium-dependent activation of fast synaptic vesicle fusion by binding Ca\(^{2+}\) and acidic phospholipids, displacing complexin from the SNARE complex, and enabling SNARE-mediated membrane fusion[1][3].