Calcium-dependent docking of synaptic vesicles. Issue 7 (July 2021)

• Record Type: Journal Article
• Authors: Silva, Melissa; Tran, Van; Marty, Alain
• Is Part Of: Trends in neurosciences. Volume 44:Issue 7(2021)
• Page Start: 579
• Page End: 592
• Publication Date: 2021-07
• Subjects: short-term synaptic plasticity -- synaptic vesicles -- SNARE proteins -- synaptotagmin -- vesicle docking -- active zone; Neurology -- Periodicals; Neurophysiology -- Periodicals; Neurobiology -- Periodicals; 612.8
• DOI: 10.1016/j.tins.2021.04.003
• Languages: English
• ISSNs: 0166-2236

Abstract

Abstract : The concentration of calcium ions in presynaptic terminals regulates transmitter release, but underlying mechanisms have remained unclear. Here we review recent studies that shed new light on this issue. Fast-freezing electron microscopy and total internal reflection fluorescence microscopy studies reveal complex calcium-dependent vesicle movements including docking on a millisecond time scale. Recordings from so-called 'simple synapses' indicate that calcium not only triggers exocytosis, but also modifies synaptic strength by controlling a final, rapid vesicle maturation step before release. Molecular studies identify several calcium-sensitive domains on Munc13 and on synaptotagmin-1 that are likely involved in bringing the vesicular and plasma membranes closer together in response to calcium elevation. Together, these results suggest that calcium-dependent vesicle docking occurs in a wide range of time domains and plays a crucial role in several phenomena including synaptic facilitation, post-tetanic potentiation, and neuromodulator-induced potentiation. Highlights: High-pressure electron microscopy reveals numerous tethers linking synaptic vesicles with neighboring vesicles and with the active zone plasma membrane. Time-resolved electron microscopy and total internal reflection microscopy studies reveal fast calcium-dependent attachment of synaptic vesicles to the active zone membrane. Simple synapse electrophysiological recordings suggest a sequential model of vesicular docking, with a fast, last docking step occurring within a few milliseconds. Molecular studies point at specific domains of Munc13 and of synaptotagmin-1 as likely contributors to calcium-dependent docking. A new model of synaptic plasticity emerges where calcium-dependent vesicular docking acts to enhance synaptic strength. This mechanism occurs over a variety of time domains, and it likely contributes to synaptic facilitation, post-tetanic potentiation, and depolarization-induced potentiation.