Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
Erica Tagliatti, Oscar D. Bello, Philipe R. F. Mendonça, Dimitrios Kotzadimitriou, Elizabeth Nicholson, Jeff Coleman, Yulia Timofeeva, James E. Rothman, Shyam S. Krishnakumar, Kirill E. Volynski
Abstract
Significance Release of neurotransmitters relies on submillisecond coupling of synaptic vesicle fusion to the triggering signal: AP-evoked presynaptic Ca 2+ influx. The key player that controls exocytosis of the synaptic vesicle is the Ca 2+ sensor synaptotagmin 1 (Syt1). While the Ca 2+ activation of Syt1 has been extensively characterized, how Syt1 reversibly clamps vesicular fusion remains enigmatic. Here, using a targeted mutation combined with fluorescence imaging and electrophysiology, we show that the structural feature of Syt1 to self-oligomerize provides the molecular basis for clamping of spontaneous and asynchronous release but is not required for triggering of synchronous release. Our findings propose a mechanistic model that explains how Syt1 oligomers regulate different modes of transmitter release in neuronal synapses.