title: Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion.
abstract: 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 I gamma, 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.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Liang-Wei
authors.initials: LW
authors.lastname: Gong
authors.forename: Gilbert
authors.initials: G
authors.lastname: Di Paolo
authors.forename: Ester
authors.initials: E
authors.lastname: Diaz
authors.forename: Gianluca
authors.initials: G
authors.lastname: Cestra
authors.forename: Maria-Elena
authors.initials: ME
authors.lastname: Diaz
authors.forename: Manfred
authors.initials: M
authors.lastname: Lindau
authors.forename: Pietro
authors.initials: P
authors.lastname: De Camilli
authors.forename: Derek
authors.initials: D
authors.lastname: Toomre
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007700:Kinetics; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D008854:Microscopy, Electron; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D022142:Secretory Vesicles / Q000201:enzymology / Q000648:ultrastructure
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D002118:Calcium