Models of synaptotagmin‐1 to trigger Ca2+‐dependent vesicle fusion

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Abstract
Vesicles in neurons and neuroendocrine cells store neurotransmitters and peptide hormones, which are released by vesicle fusion in response to Ca2+‐evoking stimuli. Synaptotagmin‐1 (Syt1), a Ca2+ sensor, mediates ultrafast exocytosis in neurons and neuroendocrine cells. After vesicle docking, Syt1 has two main groups of binding partners: anionic phospholipids and the SNARE (soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors) complex. The molecular mechanisms by which Syt1 triggers vesicle fusion remain controversial. This Review introduces and summarizes six molecular models of Syt1: (a) Syt1 triggers SNARE unclamping by displacing complexin, (b) Syt1 clamps SNARE zippering, (c) Syt1 causes membrane curvature, (d) membrane bridging by Syt1, (e) Syt1 is a vesicle‐plasma membrane distance regulator, and (f) Syt1 undergoes circular oligomerization. We discuss important conditions to test Syt1 activity in vitro and attempt to illustrate the possible roles of Syt1.
Funding Information
  • EMBO (3265)
  • National Research Foundation of Korea (NRF-2017R1A6A3A03010747)

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