Phospholipase D1: a key factor for the exocytotic machinery in neuroendocrine cells

EMBO J. 2001 May 15;20(10):2424-34. doi: 10.1093/emboj/20.10.2424.

Abstract

Phospholipase D (PLD) has been proposed to mediate cytoskeletal remodeling and vesicular trafficking along the secretory pathway. We recently described the activation of an ADP ribosylation factor-regulated PLD at the plasma membrane of chromaffin cells undergoing secretagogue-stimulated exocytosis. We show here that the isoform involved is PLD1b, and, using a real-time assay for individual cells, that PLD activation and exocytosis are closely correlated. Moreover, overexpressed PLD1, but not PLD2, increases stimulated exocytosis in a phosphatidylinositol 4,5-bisphosphate-dependent manner, whereas catalytically inactive PLD1 inhibits it. These results provide the first direct evidence that PLD1 is an important component of the exocytotic machinery in neuroendocrine cells.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Catalysis
  • Cattle
  • Cells, Cultured
  • Chromaffin Cells / cytology
  • Chromaffin Cells / enzymology*
  • Chromaffin Cells / physiology
  • Enzyme Inhibitors / pharmacology
  • Exocytosis / physiology*
  • Intracellular Fluid / enzymology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Neurosecretory Systems / cytology
  • PC12 Cells
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Phospholipase D / antagonists & inhibitors
  • Phospholipase D / metabolism*
  • Protein Kinase C / metabolism
  • Rats
  • Sphingosine / analogs & derivatives
  • Sphingosine / pharmacology

Substances

  • Actins
  • Enzyme Inhibitors
  • Isoenzymes
  • N-acetylsphingosine
  • Phosphatidylinositol 4,5-Diphosphate
  • Protein Kinase C
  • Phospholipase D
  • phospholipase D1
  • Sphingosine