Synaptotagmin-1

Synaptotagmin-1 (SYT1) is a calcium sensor protein that functions as a molecular trigger for neurotransmitter release at synapses (UniProt: P21579). It mediates calcium-dependent interactions with phospholipids and regulatory proteins including syntaxin, neurexins, and AP2, and participates in synaptic vesicle trafficking at the active zone.

SYT1 is expressed in neural tissue where it plays a critical role in synaptic transmission. A missense variant in SYT1 causes Baker-Gordon syndrome, a neurodevelopmental disorder marked by infantile hypotonia, developmental delay, and behavioral abnormalities (UniProt: P21579). The protein's central function in vesicular neurotransmission positions it as a key component of synaptic integrity.

In Alzheimer's Disease, SYT1 is down-regulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.56 across analyzed subcellular fractions (Chaparral AD proteomics). This reduction is consistent with documented synaptic dysfunction and loss in AD pathology.