title: Cdc42 facilitates invasion but not the actin-based motility of Shigella.
abstract: The enteric pathogen Shigella utilizes host-encoded proteins to invade the gastrointestinal tract. Efficient invasion of host cells requires the stimulation of Rho-family GTPases and cytoskeletal alterations by Shigella-encoded IpaC. Following invasion and lysis of the phagosome, Shigella exploits the host's actin-based polymerization machinery to assemble an actin tail that serves as the propulsive force required for spreading within and between cells. The Shigella surface protein IcsA stimulates actin-tail formation by recruiting host-encoded N-WASP to drive Arp2/3-mediated actin assembly. N-WASP is absolutely required for Shigella motility, but not for Shigella invasion. Although Rho-family GTPases have been implicated in both the invasion and motility of Shigella, the role of Cdc42, an N-WASP activator, in this process has been controversial. In these studies, we have examined the role of Cdc42 in Shigella invasion and actin-based motility using Cdc42-deficient cells. We demonstrate that Cdc42 is required for efficient Shigella invasion but reveal a minor Cdc42-independent pathway that can permit Shigella invasion. However, the actin-based motility of Shigella, as well as vaccinia, proceeds unperturbed in the absence of Cdc42. These data further support the involvement of distinct host-encoded proteins in the steps regulating invasion and intercellular spread of Shigella.
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, 55 Blossom Street, Boston, MA 02114, USA.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
mesh_terms: D000199:Actins / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D017353:Gene Deletion; D009068:Movement; D012763:Shigella flexneri / Q000254:growth & development / Q000502:physiology*; D014616:Vaccinia virus / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000199:Actins; D020764:cdc42 GTP-Binding Protein