Shigella targets epithelial tricellular junctions and uses a noncanonical clathrin-dependent endocytic pathway to spread between cells

Cell Host Microbe. 2012 Apr 19;11(4):325-36. doi: 10.1016/j.chom.2012.03.001.


Bacteria move between cells in the epithelium using a sequential pseudopodium-mediated process but the underlying mechanisms remain unclear. We show that during cell-to-cell movement, Shigella-containing pseudopodia target epithelial tricellular junctions, the contact point where three epithelial cells meet. The bacteria-containing pseudopodia were engulfed by neighboring cells only in the presence of tricellulin, a protein essential for tricellular junction integrity. Shigella cell-to-cell spread, but not pseudopodium protrusion, also depended on phosphoinositide 3-kinase, clathrin, Epsin-1, and Dynamin-2, which localized beneath the plasma membrane of the engulfing cell. Depleting tricellulin, Epsin-1, clathrin, or Dynamin-2 expression reduced Shigella cell-to-cell spread, whereas AP-2, Dab2, and Eps15 were not critical for this process. Our findings highlight a mechanism for Shigella dissemination into neighboring cells via targeting of tricellular junctions and a noncanonical clathrin-dependent endocytic pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Clathrin / metabolism*
  • Dysentery, Bacillary / metabolism
  • Dysentery, Bacillary / microbiology*
  • Dysentery, Bacillary / physiopathology*
  • Endocytosis*
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Humans
  • MARVEL Domain Containing 2 Protein
  • Membrane Proteins / metabolism
  • Shigella / physiology*
  • Tight Junctions / metabolism*
  • Tight Junctions / microbiology


  • Clathrin
  • MARVEL Domain Containing 2 Protein
  • MARVELD2 protein, human
  • Membrane Proteins