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, Josep

doi:10.7554/eLife.22567

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

Journal Article · Wed Feb 08 04:00:00 EST 2017 · eLife

DOI:https://doi.org/10.7554/eLife.22567· OSTI ID:1498359

Xu, Junjie ^[1]; Camacho, Marcial ^[2]; Xu, Yibin ^[1]; Esser, Victoria ^[1]; Liu, Xiaoxia ^[1]; Trimbuch, Thorsten ^[2]; Pan, Yun-Zu ^[1]; ^[3]; ^[4]; ^[2]; ^[1]

Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany
Key Laboratory of Molecular Biophysics of the Ministry of Education, Huazhong University of Science and Technology, Wuhan, China; College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States

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 multi-helical 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.

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: NIHFOREIGNOTHER

OSTI ID:: 1498359

Journal Information:: eLife, Journal Name: eLife Journal Issue: 02, 2017 Vol. 6; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.

Country of Publication:: United States

Language:: ENGLISH

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