A salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion

Nature. 1999 Sep 16;401(6750):293-7. doi: 10.1038/45829.

Abstract

An essential feature of the bacterial pathogen Salmonella spp. is its ability to enter cells that are normally non-phagocytic, such as those of the intestinal epithelium. The bacterium achieves entry by delivering effector proteins into the host-cell cytosol by means of a specialized protein-secretion system (termed type III), which causes reorganization of the cell's actin cytoskeleton and ruffling of its membrane. One of the bacterial effectors that stimulates these cellular responses is SopE, which acts as a guanyl-nucleotide-exchange factor on Rho GTPase proteins such as Cdc42 and Rac. As the actin-cytoskeleton reorganization induced by Salmonella is reversible and short-lived, infected cells regain their normal architecture after bacterial internalization. We show here that the S. Typhimurium effector protein SptP, which is delivered to the host-cell cytosol by the type-III secretion system, is directly responsible for the reversal of the actin cytoskeletal changes induced by the bacterium. SptP exerts this function by acting as a GTPase-activating protein (GAP) for Rac-1 and Cdc42.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Arginine / metabolism
  • Bacterial Adhesion / physiology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology*
  • Cell Cycle Proteins / metabolism*
  • Cell Membrane / microbiology
  • Escherichia coli
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • Mutation
  • Protein Kinases / metabolism
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / metabolism
  • Protein Tyrosine Phosphatases / physiology*
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism
  • Salmonella typhimurium / physiology*
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae

Substances

  • Actins
  • Bacterial Proteins
  • Cell Cycle Proteins
  • GTPase-Activating Proteins
  • Proteins
  • Recombinant Fusion Proteins
  • Arginine
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Protein Tyrosine Phosphatases
  • sptP protein, Salmonella typhimurium
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein, Saccharomyces cerevisiae