Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion.
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.
Gong
Liang-Wei
LW
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USA.
Di Paolo
Gilbert
G
Diaz
Ester
E
Cestra
Gianluca
G
Diaz
Maria-Elena
ME
Lindau
Manfred
M
De Camilli
Pietro
P
Toomre
Derek
D
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
D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase; D002118:Calcium