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 language | English (US) |
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Pages (from-to) | 2243-2248 |
Number of pages | 6 |
Journal | Current Biology |
Volume | 15 |
Issue number | 24 |
DOIs | |
State | Published - Dec 24 2005 |
Externally published | Yes |
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thank Dieter Bruns for stimulating discussions; Detlef Hof for help with data analysis; Josh Kaplan for sharing unpublished data; and Fritz Benseler, Carolin Bick, Ulrike Klemstein, Manuela Schneider, Ivonne Thanhäuser, and Reiko Trautmann for expert technical assistance.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.).