Phosphatidylinositol phosphate kinase type I gamma regulates dynamics of large dense-core vesicle fusion

Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5204-9. doi: 10.1073/pnas.0501412102. Epub 2005 Mar 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Cells, Cultured
  • Chromaffin Cells / drug effects
  • Chromaffin Cells / enzymology*
  • Chromaffin Cells / ultrastructure
  • Exocytosis / drug effects
  • Exocytosis / physiology
  • In Vitro Techniques
  • Kinetics
  • Membrane Fusion / physiology
  • Mice
  • Microscopy, Electron
  • Phosphotransferases (Alcohol Group Acceptor) / deficiency
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Secretory Vesicles / enzymology
  • Secretory Vesicles / ultrastructure

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • 1-phosphatidylinositol-4-phosphate 5-kinase
  • Calcium