| First Author | Deák F | Year | 2009 |
| Journal | J Cell Biol | Volume | 184 |
| Issue | 5 | Pages | 751-64 |
| PubMed ID | 19255244 | Mgi Jnum | J:146215 |
| Mgi Id | MGI:3837053 | Doi | 10.1083/jcb.200812026 |
| Citation | Deak F, et al. (2009) Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming. J Cell Biol 184(5):751-64 |
| abstractText | 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 Ca(2+)-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 Ca(2+) triggering of fusion. |
