Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles

被引：0
作者：
Enqi He
Keimpe Wierda
Rhode van Westen
Jurjen H. Broeke
Ruud F. Toonen
L. Niels Cornelisse
Matthijs Verhage
机构：
[1] Center for Neurogenomics and Cognitive Research,Department of Functional Genomics
[2] Neuroscience Campus Amsterdam,Department of Clinical Genetics
[3] Vrije Universiteit (VU),undefined
[4] Center for Neurogenomics and Cognitive Research,undefined
[5] Neuroscience Campus Amsterdam,undefined
[6] VU Medical Center,undefined
[7] Present address: VIB Center for the Biology of Disease,undefined
[8] Leuven 3000,undefined
[9] Belgium; Center for Human Genetics,undefined
[10] KU Leuven,undefined
[11] 3000 Leuven,undefined
[12] Belgium,undefined
来源：
Nature Communications | / 8卷
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摘要：
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.
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