Synaptotagmins: Beyond Presynaptic Neurotransmitter Release

Synaptotagmins (Syts) are well-established primary Ca²⁺ sensors to initiate presynaptic neurotransmitter release. They also play critical roles in the docking, priming, and fusion steps of exocytosis, as well as the tightly coupled exo-endocytosis, in presynapses. A recent study by Awasthi and others (2019) shows that Syt3 Ca²⁺-dependently modulates the postsynaptic receptor endocytosis and thereby promotes the long-term depression (LTD) and the decay of long-term potentiation (LTP). This work highlights the importance of Syt3 in modulating long-term synaptic plasticity and, importantly, extends the function of Syt proteins from presynaptic neurotransmitter release to a new promising postsynaptic receptor internalization.