Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission

M. Meijer; P. Burkhardt; H. de Wit; R.F.G. Toonen; D. Fasshauer; M. Verhage

doi:10.1038/emboj.2012.72

Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission

M. Meijer, P. Burkhardt, H. de Wit, R.F.G. Toonen, D. Fasshauer, M. Verhage

Functional Genomics

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission. © 2012 European Molecular Biology Organization | All Rights Reserved.

Original language	English
Pages (from-to)	2156-2168
Journal	EMBO Journal
Volume	31
Issue number	9
DOIs	https://doi.org/10.1038/emboj.2012.72
Publication status	Published - 2012

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title = "Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission",

abstract = "Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission. {\textcopyright} 2012 European Molecular Biology Organization | All Rights Reserved.",

author = "M. Meijer and P. Burkhardt and {de Wit}, H. and R.F.G. Toonen and D. Fasshauer and M. Verhage",

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T1 - Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission

AU - Meijer, M.

AU - Burkhardt, P.

AU - de Wit, H.

AU - Toonen, R.F.G.

AU - Fasshauer, D.

AU - Verhage, M.

PY - 2012

Y1 - 2012

N2 - Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission. © 2012 European Molecular Biology Organization | All Rights Reserved.

AB - Synaptic transmission depends critically on the Sec1p/Munc18 protein Munc18-1, but it is unclear whether Munc18-1 primarily operates as a integral part of the fusion machinery or has a more upstream role in fusion complex assembly. Here, we show that point mutations in Munc18-1 that interfere with binding to the free Syntaxin1a N-terminus and strongly impair binding to assembled SNARE complexes all support normal docking, priming and fusion of synaptic vesicles, and normal synaptic plasticity in munc18-1 null mutant neurons. These data support a prevailing role of Munc18-1 before/during SNARE-complex assembly, while its continued association to assembled SNARE complexes is dispensable for synaptic transmission. © 2012 European Molecular Biology Organization | All Rights Reserved.

U2 - 10.1038/emboj.2012.72

DO - 10.1038/emboj.2012.72

M3 - Article

VL - 31

SP - 2156

EP - 2168

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 9

ER -

Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission

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