ATP-mediated Erk1/2 activation stimulates bacterial capture by filopodia, which precedes Shigella invasion of epithelial cells

Cell Host Microbe. 2011 Jun 16;9(6):508-19. doi: 10.1016/j.chom.2011.05.005.

Abstract

Shigella, the causative agent of bacillary dysentery in humans, invades epithelial cells, using a type III secretory system (T3SS) to inject bacterial effectors into host cells and remodel the actin cytoskeleton. ATP released through connexin hemichanels on the epithelial membrane stimulates Shigella invasion and dissemination in epithelial cells. Here, we show that prior to contact with the cell body, Shigella is captured by nanometer-thin micropodial extensions (NMEs) at a distance from the cell surface, in a process involving the T3SS tip complex proteins and stimulated by ATP- and connexin-mediated signaling. Upon bacterial contact, NMEs retract, bringing bacteria in contact with the cell body, where invasion occurs. ATP stimulates Erk1/2 activation, which controls actin retrograde flow in NMEs and their retraction. These findings reveal previously unappreciated facets of interaction of an invasive bacterium with host cells and a prominent role for Erk1/2 in the control of filopodial dynamics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cell Line
  • Dysentery, Bacillary / enzymology*
  • Dysentery, Bacillary / metabolism
  • Dysentery, Bacillary / microbiology*
  • Dysentery, Bacillary / physiopathology
  • Enzyme Activation
  • Epithelial Cells / enzymology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Host-Pathogen Interactions*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Pseudopodia / enzymology
  • Pseudopodia / metabolism
  • Pseudopodia / microbiology*
  • Shigella / genetics
  • Shigella / physiology*
  • Signal Transduction

Substances

  • Bacterial Proteins
  • Adenosine Triphosphate
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3