Munc18-1 stabilizes syntaxin 1, but is not essential for syntaxin 1 targeting and SNARE complex formation
| Autor: | Ruud F G, Toonen, Klaas Jan, de Vries, Robbert, Zalm, Thomas C, Südhof, Matthijs, Verhage |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Mice Knockout Macromolecular Substances Presynaptic Terminals Synaptic Membranes Vesicular Transport Proteins Brain Syntaxin 1 Nerve Tissue Proteins Membrane Fusion Synaptic Transmission Exocytosis Cell Line Mice Inbred C57BL Mice Protein Transport Munc18 Proteins Antigens Surface Animals Humans Female SNARE Proteins Molecular Chaperones |
| Zdroj: | Journal of neurochemistry. 93(6) |
| ISSN: | 0022-3042 |
| Popis: | Munc18-1, a member of the Sec1/Munc18 (SM) protein family, is essential for synaptic vesicle exocytosis. Munc18-1 binds tightly to the SNARE protein syntaxin 1, but the physiological significance and functional role of this interaction remain unclear. Here we show that syntaxin 1 levels are reduced by 70% in munc18-1 knockout mice. Pulse-chase analysis in transfected HEK293 cells revealed that Munc18-1 directly promotes the stability of syntaxin 1, consistent with a chaperone function. However, the residual syntaxin 1 in munc18-1 knockout mice is still correctly targeted to synapses and efficiently forms SDS-resistant SNARE complexes, demonstrating that Munc18-1 is not required for syntaxin 1 function as such. These data demonstrate that the Munc18-1 interaction with syntaxin 1 is physiologically important, but does not represent a classical chaperone-substrate relationship. Instead, the presence of SNARE complexes in the absence of membrane fusion in munc18-1 knockout mice indicates that Munc18-1 either controls the spatially correct assembly of core complexes for SNARE-dependent fusion, or acts as a direct component of the fusion machinery itself. |
| Databáze: | OpenAIRE |
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