Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release

TAGLIATTI, ERICA; KOTZADIMITRIOU, DIMITRIOS; TIMOFEEVA, YULIA; VOLYNSKI, KIRILL E.; MENDONÇA, PHILIPE R. F.; COLEMAN, JEFF; KRISHNAKUMAR, SHYAM S.; BELLO, OSCAR D.; NICHOLSON, ELIZABETH; ROTHMAN, JAMES E.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Año: 2020 vol. 117 p. 3819 - 3827

0027-8424

Release of neurotransmitters relies on submillisecond coupling of synaptic vesicle fusion to the triggering signal: AP-evoked presynaptic Ca2+ influx. The key player that controls exocytosis of the synaptic vesicle is the Ca2+ sensor synaptotagmin 1 (Syt1). While the Ca2+ 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.