| First Author | Gerber SH | Year | 2008 |
| Journal | Science | Volume | 321 |
| Issue | 5895 | Pages | 1507-10 |
| PubMed ID | 18703708 | Mgi Jnum | J:138035 |
| Mgi Id | MGI:3803800 | Doi | 10.1126/science.1163174 |
| Citation | Gerber SH, et al. (2008) Conformational Switch of Syntaxin-1 Controls Synaptic Vesicle Fusion. Science 321(5895):1507-10 |
| abstractText | During synaptic vesicle fusion, the SNARE-protein syntaxin-1 exhibits two conformations that both bind to Munc18-1: a 'closed' conformation outside the SNARE-complex, and an 'open' conformation in the SNARE-complex. Whereas SNARE-complexes containing 'open' syntaxin-1 and Munc18-1 are essential for exocytosis, the significance of 'closed' syntaxin-1 is unknown. Here, we generated knockin/knockout mice that expressed only 'open' syntaxin-1B. Syntaxin-1B(Open) mice were viable, but succumbed to generalized seizures at 2 to 3 months of age. Binding of Munc18-1 to syntaxin-1 was impaired in syntaxin-1B(Open) synapses, and the size of the readily releasable vesicle pool was decreased, whereas the rate of synaptic vesicle fusion was dramatically enhanced. Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies. |
