The diversity of synaptotagmin isoforms

The synaptotagmin family of molecules is known for regulating calcium-dependent membrane fusion events. Mice and humans express 17 synaptotagmin isoforms, where most studies have focused on isoforms 1, 2, and 7, which are involved in synaptic vesicle exocytosis. Recent work has highlighted how brain function relies on additional isoforms, with roles in postsynaptic receptor endocytosis, vesicle trafficking, membrane repair, synaptic plasticity, and protection against neurodegeneration, for example, in addition to the traditional concept of synaptotagmin-mediated neurotransmitter release - in neurons as well as glia, and at different timepoints. In fact, it is not uncommon for the same isoform to feature several splice isoforms, form homo- and heterodimers, and function in different subcellular locations and cell types. This review aims to highlight the diversity of synaptotagmins, offers a concise summary of key findings on all isoforms, and discusses different ways of grouping these.