Phosphatidylinositol 4,5-bisphosphate regulates SNARE-dependent membrane fusion
| Autor: | Judith A. Kowalchyk, Declan J. James, Thomas Martin, Chuenchanok Khodthong |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Phosphatidylinositol 4
5-Diphosphate Vesicle fusion Syntaxin 1 Biology Membrane Fusion PC12 Cells Article Exocytosis 03 medical and health sciences chemistry.chemical_compound Membrane Microdomains 0302 clinical medicine Animals Transport Vesicles Research Articles 030304 developmental biology 0303 health sciences Dose-Response Relationship Drug Cell Membrane Lipid bilayer fusion SNAP25 Munc-18 Cell Biology Rats Cell biology Phosphatidylinositol 4 5-bisphosphate chemistry Liposomes Soluble NSF attachment protein SNARE Proteins 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.200801056 |
| Popis: | Phosphatidylinositol 4,5-bisphosphate (PI 4,5-P(2)) on the plasma membrane is essential for vesicle exocytosis but its role in membrane fusion has not been determined. Here, we quantify the concentration of PI 4,5-P(2) as approximately 6 mol% in the cytoplasmic leaflet of plasma membrane microdomains at sites of docked vesicles. At this concentration of PI 4,5-P(2) soluble NSF attachment protein receptor (SNARE)-dependent liposome fusion is inhibited. Inhibition by PI 4,5-P(2) likely results from its intrinsic positive curvature-promoting properties that inhibit formation of high negative curvature membrane fusion intermediates. Mutation of juxtamembrane basic residues in the plasma membrane SNARE syntaxin-1 increase inhibition by PI 4,5-P(2), suggesting that syntaxin sequesters PI 4,5-P(2) to alleviate inhibition. To define an essential rather than inhibitory role for PI 4,5-P(2), we test a PI 4,5-P(2)-binding priming factor required for vesicle exocytosis. Ca(2+)-dependent activator protein for secretion promotes increased rates of SNARE-dependent fusion that are PI 4,5-P(2) dependent. These results indicate that PI 4,5-P(2) regulates fusion both as a fusion restraint that syntaxin-1 alleviates and as an essential cofactor that recruits protein priming factors to facilitate SNARE-dependent fusion. |
| Databáze: | OpenAIRE |
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