Synaptotagmin-12 (Syt12) belongs to the synaptotagmin family, which is a group of membrane-trafficking proteins that contain two C-terminal C2 domains (known as C2A and C2B domains). Most of the synaptotagmins have a unique N-terminal domain that is involved in membrane anchoring or specific ligand binding. Mammals contain 16 synaptotagmins; eight of these bind Ca2+ via their C2-domains (Syt1-Syt3, Syt5-7, Syt9, and Syt10), whereas the other eight, including Syt12, do not [].Syt12 colocalises with and binds Syt1 on synaptic vesicles, but regulates spontaneous release independently from Syt1. Syt12 is phosphorylated by cAMP-dependent protein kinase A (PKA) at a single site, and mutation of this site blocks the effect of Syt12 on spontaneous release []. Syt12 is not essential for basal synaptic transmission, but is required for cAMP-dependent mossy fibre long-term potentiation (LTP), a presynaptic form of long-term plasticity that is induced by PKA activation [].
