Synapsin

Synapsins are a family of neuron-specific phosphoproteins that associate with the cytoplasmic surface of synaptic vesicles in presynaptic terminals. The family comprises Synapsin I, II, and III, encoded by the SYN1, SYN2, and SYN3 genes. Synapsins are abundantly expressed in the vertebrate brain and function as vesicle-associated proteins that also interact with the actin cytoskeleton and with phospholipids at the vesicle membrane.

In the presynaptic terminal, synapsins help tether synaptic vesicles to each other and to the cytoskeleton, shaping the vesicle reserve pool and regulating vesicle availability for release. They play a regulatory role in neurotransmitter exocytosis, particularly during sustained or high-frequency activity. The dynamic association of synapsins with vesicles is controlled by phosphorylation: diverse kinases, including PKA, CaMKII, and MAP kinases, phosphorylate synapsins in response to neuronal activity, decreasing vesicle tethering and promoting mobilization of vesicles toward release sites.

Synapsin function is conserved across vertebrates, and alterations to synapsin genes affect synaptic transmission. In animal models, loss of synapsin function produces altered neurotransmitter release and seizure susceptibility. In humans, variants in SYN1 have been associated with epilepsy and neurodevelopmental disorders such as autism spectrum disorders, though such variants are rare. The roles of SYN2 and SYN3 in human disease are less well defined.