Back to Search
Start Over
Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming
- Source :
- The Journal of Cell Biology
- Publication Year :
- 2009
- Publisher :
- The Rockefeller University Press, 2009.
-
Abstract
- Munc18-1 and soluble NSF attachment protein receptors (SNAREs) are critical for synaptic vesicle fusion. Munc18-1 binds to the SNARE syntaxin-1 folded into a closed conformation and to SNARE complexes containing open syntaxin-1. Understanding which steps in fusion depend on the latter interaction and whether Munc18-1 competes with other factors such as complexins for SNARE complex binding is critical to elucidate the mechanisms involved. In this study, we show that lentiviral expression of Munc18-1 rescues abrogation of release in Munc18-1 knockout mice. We describe point mutations in Munc18-1 that preserve tight binding to closed syntaxin-1 but markedly disrupt Munc18-1 binding to SNARE complexes containing open syntaxin-1. Lentiviral rescue experiments reveal that such disruption selectively impairs synaptic vesicle priming but not Ca2+-triggered fusion of primed vesicles. We also find that Munc18-1 and complexin-1 bind simultaneously to SNARE complexes. These results suggest that Munc18-1 binding to SNARE complexes mediates synaptic vesicle priming and that the resulting primed state involves a Munc18-1–SNARE–complexin macromolecular assembly that is poised for Ca2+ triggering of fusion.
- Subjects :
- Vesicle fusion
Macromolecular Substances
Genetic Vectors
Presynaptic Terminals
Synaptic Membranes
Syntaxin 1
Nerve Tissue Proteins
Biology
Transfection
Membrane Fusion
Synaptic Transmission
Article
Mice
Munc18 Proteins
Animals
Point Mutation
Research Articles
Cells, Cultured
Mice, Knockout
STX1A
SNAP25
Brain
Munc-18
Cell Biology
Kiss-and-run fusion
Cell biology
Rats
Adaptor Proteins, Vesicular Transport
Soluble NSF attachment protein
Synaptic Vesicles
biological phenomena, cell phenomena, and immunity
SNARE complex
SNARE Proteins
Synaptic vesicle priming
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 15408140 and 00219525
- Volume :
- 184
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....d92172ec16feb4434df1256bf6854702