title: Shigella targets epithelial tricellular junctions and uses a noncanonical clathrin-dependent endocytic pathway to spread between cells.
abstract: 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.
authors.affiliation: Department of Infectious Disease Control, International Research Center for Infectious Disease, University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Fukumatsu
authors.forename: Michinaga
authors.initials: M
authors.lastname: Ogawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Arakawa
authors.forename: Masato
authors.initials: M
authors.lastname: Suzuki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakayama
authors.forename: Shigeomi
authors.initials: S
authors.lastname: Shimizu
authors.forename: Minsoo
authors.initials: M
authors.lastname: Kim
authors.forename: Hitomi
authors.initials: H
authors.lastname: Mimuro
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D000818:Animals; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D004405:Dysentery, Bacillary / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology*; D004705:Endocytosis; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D062794:MARVEL Domain Containing 2 Protein; D008565:Membrane Proteins / Q000378:metabolism; D012760:Shigella / Q000502:physiology*; D019108:Tight Junctions / Q000378:metabolism* / Q000382:microbiology
chemical_list: D002966:Clathrin; D062794:MARVEL Domain Containing 2 Protein; C516798:MARVELD2 protein, human; D008565:Membrane Proteins