Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN

Junjie Xu, Marcial Camacho, Yibin Xu, Victoria Esser, Xiaoxia Liu, Thorsten Trimbuch, Yun Zu Pan, Cong Ma, Diana R Tomchick, Christian Rosenmund, Jose Rizo-Rey

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Munc13–1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13–1 are coordinated. The crystal structure of a Munc13–1 fragment including its C1, C2B and MUN domains (C1C2BMUN) reveals a 19.5 nm-long multihelical structure with the C1 and C2B domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca2+-binding sites of the C1 and C2B domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13–1 by Ca2+ and diacylglycerol during short-term presynaptic plasticity are closely interrelated. Electrophysiological experiments in mouse neurons support the functional importance of the domain interfaces observed in C1C2BMUN. The structure imposes key constraints for models of neurotransmitter release and suggests that Munc13–1 bridges the vesicle and plasma membranes from the periphery of the membrane-membrane interface.

Original languageEnglish (US)
Article numbere22567
JournaleLife
Volume6
DOIs
StatePublished - Feb 8 2017

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Cell membranes
Plasticity
Neurotransmitter Agents
Crystal structure
Cell Membrane
Membranes
Synaptic Vesicles
Diglycerides
Neurons
Chemical activation
Binding Sites
Experiments

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN. / Xu, Junjie; Camacho, Marcial; Xu, Yibin; Esser, Victoria; Liu, Xiaoxia; Trimbuch, Thorsten; Pan, Yun Zu; Ma, Cong; Tomchick, Diana R; Rosenmund, Christian; Rizo-Rey, Jose.

In: eLife, Vol. 6, e22567, 08.02.2017.

Research output: Contribution to journalArticle

Xu, Junjie ; Camacho, Marcial ; Xu, Yibin ; Esser, Victoria ; Liu, Xiaoxia ; Trimbuch, Thorsten ; Pan, Yun Zu ; Ma, Cong ; Tomchick, Diana R ; Rosenmund, Christian ; Rizo-Rey, Jose. / Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN. In: eLife. 2017 ; Vol. 6.
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AU - Trimbuch, Thorsten

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