Conversion of PtdIns(4,5)P(2) Into PtdIns(5)P by the S.flexneri Effector IpgD Reorganizes Host Cell Morphology

EMBO J. 2002 Oct 1;21(19):5069-78. doi: 10.1093/emboj/cdf522.

Abstract

Phosphoinositides play a central role in the control of several cellular events including actin cytoskeleton organization. Here we show that, upon infection of epithelial cells with the Gram-negative pathogen Shigella flexneri, the virulence factor IpgD is translocated directly into eukaryotic cells and acts as a potent inositol 4-phosphatase that specifically dephosphorylates phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] into phosphatidylinositol 5-monophosphate [PtdIns(5)P] that then accumulates. Transfection experiments indicate that the transformation of PtdIns(4,5)P(2) into PtdIns(5)P by IpgD is responsible for dramatic morphological changes of the host cell, leading to a decrease in membrane tether force associated with membrane blebbing and actin filament remodelling. These data provide the molecular basis for a new mechanism employed by a pathogenic bacterium to promote membrane ruffling at the entry site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Bacterial Proteins / metabolism*
  • Cell Adhesion
  • Enzyme Activation
  • HeLa Cells
  • Humans
  • Kinetics
  • Mice
  • Mutagenesis, Site-Directed
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism*
  • Phosphatidylinositol Phosphates / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism*
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / metabolism
  • Shigella flexneri / enzymology*
  • Transfection

Substances

  • Bacterial Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Recombinant Fusion Proteins
  • phosphatidylinositol 5-phosphate
  • Phosphatidylinositol 3-Kinases
  • IpgD protein, Shigella flexneri
  • Phosphoric Monoester Hydrolases