@article{0eb2ac0756a145f9a62939686bd0b701,
title = "Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles",
abstract = "Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds. Munc13-1 deficiency produces a similar defect. Inhibitors of N-ethylmaleimide sensitive factor (NSF), N-ethylmaleimide (NEM) or interfering peptides, prevent de-priming in munc18-1/2SWAP or munc13-1 null synapses, but not in CAPS-1/2 null, another priming-deficient mutant. NEM rescues synaptic transmission in munc13-1 null and munc18-1/2SWAP synapses, in acute munc13-1 null slices and even partially in munc13-1/2 double null synapses. Together these data indicate that Munc13-1 and Munc18-1, but not CAPS-1/2, stabilize primed synaptic vesicles by preventing NSF-dependent de-priming.",
keywords = "Journal Article",
author = "Enqi He and Keimpe Wierda and {van Westen}, Rhode and Broeke, {Jurjen H} and Toonen, {Ruud F} and Cornelisse, {L Niels} and Matthijs Verhage",
year = "2017",
month = jun,
day = "21",
doi = "10.1038/ncomms15915",
language = "English",
volume = "8",
pages = "15915",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}
