Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN
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 it...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/22567 |
| _version_ | 1818028233448226816 |
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| author | Junjie Xu Marcial Camacho Yibin Xu Victoria Esser Xiaoxia Liu Thorsten Trimbuch Yun-Zu Pan Cong Ma Diana R Tomchick Christian Rosenmund Josep Rizo |
| author_facet | Junjie Xu Marcial Camacho Yibin Xu Victoria Esser Xiaoxia Liu Thorsten Trimbuch Yun-Zu Pan Cong Ma Diana R Tomchick Christian Rosenmund Josep Rizo |
| author_sort | Junjie Xu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:00:32Z |
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| id | doaj.art-482920feddd245e689ecabf30e55ff0b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:00:32Z |
| publishDate | 2017-02-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-482920feddd245e689ecabf30e55ff0b2022-12-22T02:01:24ZengeLife Sciences Publications LtdeLife2050-084X2017-02-01610.7554/eLife.22567Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUNJunjie Xu0Marcial Camacho1Yibin Xu2Victoria Esser3Xiaoxia Liu4Thorsten Trimbuch5Yun-Zu Pan6Cong Ma7https://orcid.org/0000-0002-7814-0500Diana R Tomchick8https://orcid.org/0000-0002-7529-4643Christian Rosenmund9https://orcid.org/0000-0002-3905-2444Josep Rizo10https://orcid.org/0000-0003-1773-8311Department 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 StatesDepartment of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, GermanyDepartment 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 StatesDepartment 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 StatesDepartment 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 StatesDepartment of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, GermanyDepartment 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 StatesKey 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, ChinaDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States; Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, GermanyDepartment 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 StatesMunc13–1 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.https://elifesciences.org/articles/22567neurotransmitter releaseMunc13presynaptic plasticitysynaptic vesicle fusioncalcium binding |
| spellingShingle | Junjie Xu Marcial Camacho Yibin Xu Victoria Esser Xiaoxia Liu Thorsten Trimbuch Yun-Zu Pan Cong Ma Diana R Tomchick Christian Rosenmund Josep Rizo Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN eLife neurotransmitter release Munc13 presynaptic plasticity synaptic vesicle fusion calcium binding |
| title | Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN |
| title_full | Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN |
| title_fullStr | Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN |
| title_full_unstemmed | Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN |
| title_short | Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN |
| title_sort | mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of munc13 1 c1c2bmun |
| topic | neurotransmitter release Munc13 presynaptic plasticity synaptic vesicle fusion calcium binding |
| url | https://elifesciences.org/articles/22567 |
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