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RESEARCH PRODUCT
Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion.
Gianluca CestraManfred LindauLiang Wei GongPietro De CamilliGilbert Di PaoloE. DiazDerek ToomreM. E. Díazsubject
Vesicle fusionChromaffin CellsBiologyIn Vitro TechniquesMembrane FusionExocytosisExocytosischemistry.chemical_compoundMiceAnimalsPhosphatidylinositolCells CulturedMultidisciplinaryVesicleSecretory VesiclesSNAP25Munc-18Kiss-and-run fusionBiological SciencesSecretory VesicleCell biologyKineticsMicroscopy ElectronPhosphotransferases (Alcohol Group Acceptor)chemistryCalciumdescription
Phosphatidylinositol-4,5-bisphosphate was proposed to be an important regulator of large dense-core vesicle exocytosis from neuroendocrine tissues. Here, we have examined the kinetics of secretion in chromaffin cells from mice lacking phosphatidylinositol phosphate kinase type Iγ, the major neuronal phosphatidylinositol-4-phosphate 5-kinase. Absence of this enzyme caused a reduction of the readily releasable vesicle pool and its refilling rate, with a small increase in morphologically docked vesicles, indicating a defect in vesicle priming. Furthermore, amperometry revealed a delay in fusion pore expansion. These results provide direct genetic evidence for a key role of phosphatidylinositol-4,5-bisphosphate synthesis in the regulation of large dense-core vesicle fusion dynamics.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2005-04-05 | Proceedings of the National Academy of Sciences of the United States of America |