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Publication

Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18.

Neuron | 2017

Munc13 catalyzes the transit of syntaxin from a closed complex with Munc18 into the ternary SNARE complex. Here we report a new function of Munc13, independent of Munc18: it promotes the proper syntaxin/synaptobrevin subconfiguration during assembly of the ternary SNARE complex. In cooperation with Munc18, Munc13 additionally ensures the proper syntaxin/SNAP-25 subconfiguration. In a reconstituted fusion assay with SNAREs, complexin, and synaptotagmin, inclusion of both Munc13 and Munc18 quadruples the Ca2+-triggered amplitude and achieves Ca2+ sensitivity at near-physiological concentrations. In Munc13-1/2 double-knockout neurons, expression of a constitutively open mutant of syntaxin could only minimally restore neurotransmitter release relative to Munc13-1 rescue. Together, the physiological functions of Munc13 may be related to regulation of proper SNARE complex assembly.

Pubmed ID: 28772123 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

GraphPad Prism (RRID:SCR_002798)

Antibodies used in this publication

Associated grants

Agency: Howard Hughes Medical Institute, United States
Agency: NIA NIH HHS, United States
Id: P50 AG047366
Agency: NIMH NIH HHS, United States
Id: R37 MH063105

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This is a list of tools and resources that we have found mentioned in this publication.

GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Goat Anti-Mouse IgG (H+L) (Min X Bv Ch Gt GP Ham Hs Hu Rb Rt & Sh Serum Proteins) Antibody, IRDYE700DX Conjugated (antibody)

RRID:AB_220121

This unknown targets Mouse IgG (H&L)

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RABBIT IgG (H&L) Antibody IRDye800 Conjugated Pre-adsorbed (antibody)

RRID:AB_220152

This polyclonal targets RABBIT IgG (H&L) IRDye800 Pre-adsorbed

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Monoclonal Anti-beta-Tubulin antibody produced in mouse (antibody)

RRID:AB_477577

This monoclonal targets beta-Tubulin

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Anti-Munc 13-1 (antibody)

RRID:AB_887733

This polyclonal targets Munc 13-1

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Anti-Syntaxin 1 (antibody)

RRID:AB_887842

This monoclonal targets Syntaxin 1

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Rabbit Anti-Actin, aa 20-33 Antibody, Unconjugated (antibody)

RRID:AB_476738

This unknown targets Actin, aa 20-33

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MATLAB (software resource)

RRID:SCR_001622

Multi paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.

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