Microsecond dissection of neurotransmitter release: SNARE-complex assembly dictates speed and Ca²⁺ sensitivity.

TitleMicrosecond dissection of neurotransmitter release: SNARE-complex assembly dictates speed and Ca²⁺ sensitivity.
Publication TypeJournal Article
Year of Publication2014
AuthorsAcuna C, Guo Q, Burré J, Sharma M, Sun J, Südhof TC
JournalNeuron
Volume82
Issue5
Pagination1088-100
Date Published2014 Jun 04
ISSN1097-4199
KeywordsAnimals, Calcium, Glutamic Acid, HEK293 Cells, Humans, Membrane Fusion, Mice, Mice, Transgenic, Neurons, SNARE Proteins, Synaptic Transmission, Synaptic Vesicles, Syntaxin 1
Abstract

SNARE-complex assembly mediates synaptic vesicle fusion during neurotransmitter release and requires that the target-SNARE protein syntaxin-1 switches from a closed to an open conformation. Although many SNARE proteins are available per vesicle, only one to three SNARE complexes are minimally needed for a fusion reaction. Here, we use high-resolution measurements of synaptic transmission in the calyx-of-Held synapse from mutant mice in which syntaxin-1 is rendered constitutively open and SNARE-complex assembly is enhanced to examine the relation between SNARE-complex assembly and neurotransmitter release. We show that enhancing SNARE-complex assembly dramatically increases the speed of evoked release, potentiates the Ca(2+)-affinity of release, and accelerates fusion-pore expansion during individual vesicle fusion events. Our data indicate that the number of assembled SNARE complexes per vesicle during fusion determines the presynaptic release probability and fusion kinetics and suggest a mechanism whereby proteins (Munc13 or RIM) may control presynaptic plasticity by regulating SNARE-complex assembly.

DOI10.1016/j.neuron.2014.04.020
Alternate JournalNeuron
PubMed ID24908488
PubMed Central IDPMC4109412
Grant ListP50 MH086403 / MH / NIMH NIH HHS / United States