Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

Xiaoyu Yang, Shen Wang, Yi Sheng, Mingshu Zhang, Wenjuan Zou, Lijie Wu, Lijun Kang, Jose Rizo-Rey, Rongguang Zhang, Tao Xu, Cong Ma

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

UNC-13-Munc13s have a central function in synaptic-vesicle priming through their MUN domains. However, it is unclear whether this function arises from the ability of the MUN domain to mediate the transition from the Munc18-1-closed syntaxin-1 complex to the SNARE complex in vitro. The crystal structure of the rat Munc13-1 MUN domain now reveals an elongated, arch-shaped architecture formed by α-helical bundles, with a highly conserved hydrophobic pocket in the middle. Mutation of two residues (NF) in this pocket abolishes the stimulation caused by the Munc13-1 MUN domain on SNARE-complex assembly and on SNARE-dependent proteoliposome fusion in vitro. Moreover, the same mutation in UNC-13 abrogates synaptic-vesicle priming in Caenorhabditis elegans neuromuscular junctions. These results support the notion that orchestration of syntaxin-1 opening and SNARE-complex assembly underlies the central role of UNC-13-Munc13s in synaptic-vesicle priming.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalNature Structural and Molecular Biology
Volume22
Issue number7
DOIs
StatePublished - Jul 9 2015

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Qa-SNARE Proteins
SNARE Proteins
Synaptic Vesicles
Syntaxin 1
Mutation
Neuromuscular Junction
Caenorhabditis elegans
In Vitro Techniques

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. / Yang, Xiaoyu; Wang, Shen; Sheng, Yi; Zhang, Mingshu; Zou, Wenjuan; Wu, Lijie; Kang, Lijun; Rizo-Rey, Jose; Zhang, Rongguang; Xu, Tao; Ma, Cong.

In: Nature Structural and Molecular Biology, Vol. 22, No. 7, 09.07.2015, p. 547-554.

Research output: Contribution to journalArticle

Yang, X, Wang, S, Sheng, Y, Zhang, M, Zou, W, Wu, L, Kang, L, Rizo-Rey, J, Zhang, R, Xu, T & Ma, C 2015, 'Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming', Nature Structural and Molecular Biology, vol. 22, no. 7, pp. 547-554. https://doi.org/10.1038/nsmb.3038
Yang, Xiaoyu ; Wang, Shen ; Sheng, Yi ; Zhang, Mingshu ; Zou, Wenjuan ; Wu, Lijie ; Kang, Lijun ; Rizo-Rey, Jose ; Zhang, Rongguang ; Xu, Tao ; Ma, Cong. / Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming. In: Nature Structural and Molecular Biology. 2015 ; Vol. 22, No. 7. pp. 547-554.
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