Synaptotagmin 1 and 2 (SYT1/SYT2)

Synaptotagmin-1 (SYT1) and Synaptotagmin-2 (SYT2) are integral membrane proteins of synaptic vesicles that serve as the primary calcium sensors for fast, synchronous neurotransmitter release (UniProt P21579, Q8N9I0). In cholinergic presynaptic terminals, particularly at the neuromuscular junction, these isoforms facilitate the fusion of acetylcholine-containing vesicles with the presynaptic membrane by binding calcium through their C2 domains (PubMed: 12644833). Beyond their physiological function, SYT1 and SYT2 act as high-affinity protein receptors for Botulinum neurotoxins B and G, which exploit the vesicle recycling process to enter neurons (PubMed: 14742440). Once internalized, these toxins inhibit further acetylcholine release, leading to muscle paralysis. Clinically, these proteins are relevant in the context of botulism and autoimmune disorders like Lambert-Eaton myasthenic syndrome, where autoantibodies may target the calcium-sensing machinery (PubMed: 10859095). Therapeutic applications involve the use of botulinum toxin type B (RimabotulinumtoxinB) for conditions like cervical dystonia, leveraging the specific binding to these synaptotagmin isoforms (StatPearls: NBK557381).

Other names

SYT1SYT2Synaptotagmin-1Synaptotagmin-2P65SVP65Calcium sensor

Botulinum neurotoxins bind to the luminal domain of Synaptotagmin 1 or 2 during vesicle recycling to facilitate endocytic entry into the cholinergic terminal, where they subsequently inhibit acetylcholine release.