Identification of the minimal protein domain required for priming activity of munc13-1

David R. Stevens, Zheng Xing Wu, Ulf Matti, Harald J. Junge, Claudia Schirra, Ute Becherer, Sonja M. Wojcik, Nils Brose, Jens Rettig

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

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 [1-7]. 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 [8-13]. 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.

Original languageEnglish (US)
Pages (from-to)2243-2248
Number of pages6
JournalCurrent Biology
Volume15
Issue number24
DOIs
StatePublished - Dec 24 2005

Bibliographical note

Funding Information:
We thank Dieter Bruns for stimulating discussions; Detlef Hof for help with data analysis; Josh Kaplan for sharing unpublished data; and Fritz Benseler, Carolin Bick, Ulrike Klemstein, Manuela Schneider, Ivonne Thanhäuser, and Reiko Trautmann for expert technical assistance. This work was supported by local funding ([HOMFOR, Univ. Saarland] to U.M. and J.R.), by the Max-Planck-Society (to N.B.), and by grants from the Deutsche Forschungsgemeinschaft (SFB406/A1 to N.B. and SFB530/C9 to J.R.).

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