Identification of the minimal protein domain required for priming activity of Munc13-1 |
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Authors: | Stevens David R Wu Zheng-Xing Matti Ulf Junge Harald J Schirra Claudia Becherer Ute Wojcik Sonja M Brose Nils Rettig Jens |
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Affiliation: | 1. Physiologisches Institut, Universität des Saarlandes, Kirrberger Str. 8, D-66421 Homburg/Saar, Germany;2. Abteilung Molekulare Neurobiologie, Max-Planck-Institut für Experimentelle Medizin, D-37075 Göttingen, Germany |
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Abstract: | Most nerve cells communicate with each other through synaptic transmission at chemical synapses. The regulated exocytosis of neurotransmitters, hormones, and peptides occurs at specialized membrane areas through Ca2+-triggered fusion of secretory vesicles with the plasma membrane . Prior to fusion, vesicles are docked at the plasma membrane and must then be rendered fusion-competent through a process called priming. The molecular mechanism underlying this priming process is most likely the formation of the SNARE complex consisting of Syntaxin 1, SNAP-25, and Synaptobrevin 2. Members of the Munc13 protein family consisting of Munc13-1, -2, -3, and -4 were found to be absolutely required for this priming process . In the present study, we identified the minimal Munc13-1 domain that is responsible for its priming activity. Using Munc13-1 deletion constructs in an electrophysiological gain-of-function assay of chromaffin-granule secretion, we show that priming activity is mediated by the C-terminal residues 1100-1735 of Munc13-1, which contains both Munc13-homology domains and the C-terminal C2 domain. Priming by Munc13-1 appears to require its interaction with Syntaxin 1 because point mutants that do not bind Syntaxin 1 do not prime chromaffin granules. |
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