Title |
A C1-C2 Module in Munc13 Inhibits Calcium-Dependent Neurotransmitter Release
|
---|---|
Published in |
Neuron, August 2017
|
DOI | 10.1016/j.neuron.2017.07.015 |
Pubmed ID | |
Authors |
Francesco Michelassi, Haowen Liu, Zhitao Hu, Jeremy S. Dittman |
Abstract |
Almost all known forms of fast chemical synaptic transmission require the synaptic hub protein Munc13. This essential protein has also been implicated in mediating several forms of use-dependent plasticity, but the mechanisms by which it controls vesicle fusion and plasticity are not well understood. Using the C. elegans Munc13 ortholog UNC-13, we show that deletion of the C2B domain, the most highly conserved domain of Munc13, enhances calcium-dependent exocytosis downstream of vesicle priming, revealing a novel autoinhibitory role for the C2B. Furthermore, C2B inhibition is relieved by calcium binding to C2B, while the neighboring C1 domain acts together with C2B to stabilize the autoinhibited state. Selective disruption of Munc13 autoinhibition profoundly impacts nervous system function in vivo. Thus, C1-C2B exerts a basal inhibition on Munc13 in the primed state, permitting calcium- and lipid-dependent control of C1-C2B to modulate synaptic strength. |
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Geographical breakdown
Country | Count | As % |
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United States | 4 | 33% |
United Kingdom | 2 | 17% |
France | 1 | 8% |
Puerto Rico | 1 | 8% |
Australia | 1 | 8% |
Unknown | 3 | 25% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 7 | 58% |
Scientists | 4 | 33% |
Science communicators (journalists, bloggers, editors) | 1 | 8% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 78 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 20 | 26% |
Researcher | 16 | 21% |
Student > Bachelor | 4 | 5% |
Student > Doctoral Student | 3 | 4% |
Other | 3 | 4% |
Other | 11 | 14% |
Unknown | 21 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 23 | 29% |
Agricultural and Biological Sciences | 16 | 21% |
Biochemistry, Genetics and Molecular Biology | 14 | 18% |
Medicine and Dentistry | 2 | 3% |
Environmental Science | 1 | 1% |
Other | 1 | 1% |
Unknown | 21 | 27% |