title: Enteropathogenic Escherichia coli and vaccinia virus do not require the family of WASP-interacting proteins for pathogen-induced actin assembly.
abstract: The human pathogens enteropathogenic Escherichia coli (EPEC) and vaccinia virus trigger actin assembly in host cells by activating the host adaptor Nck and the actin nucleation promoter neural Wiskott-Aldrich syndrome protein (N-WASP). EPEC translocates effector molecules into host cells via type III secretion, and the interaction between the translocated intimin receptor (Tir) and the bacterial membrane protein intimin stimulates Nck and N-WASP recruitment, leading to the formation of actin pedestals beneath adherent bacteria. Vaccinia virus also recruits Nck and N-WASP to generate actin tails that promote cell-to-cell spread of the virus. In addition to Nck and N-WASP, WASP-interacting protein (WIP) localizes to vaccinia virus tails, and inhibition of actin tail formation upon ectopic expression of WIP mutants led to the suggestion that WIP is required for this process. Similar studies of WIP mutants, however, did not affect the ability of EPEC to form actin pedestals, arguing against an essential role for WIP in EPEC-induced actin assembly. In this study, we demonstrate that Nck and N-WASP are normally recruited by vaccinia virus and EPEC in the absence of WIP, and neither WIP nor the WIP family members CR16 and WIRE/WICH are essential for pathogen induced actin assembly. In addition, although Nck binds EPEC Tir directly, N-WASP is required for its localization during pedestal formation. Overall, these data highlight similar pathogenic strategies shared by EPEC and vaccinia virus by demonstrating a requirement for both Nck and N-WASP, but not WIP or WIP family members in pathogen-induced actin assembly.
authors.affiliation: Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Garber
authors.forename: Fuminao
authors.initials: F
authors.lastname: Takeshima
authors.forename: Inés M
authors.initials: IM
authors.lastname: Antón
authors.forename: Michiko K
authors.initials: MK
authors.lastname: Oyoshi
authors.forename: Anna
authors.initials: A
authors.lastname: Lyubimova
authors.forename: Archana
authors.initials: A
authors.lastname: Kapoor
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
authors.forename: John M
authors.initials: JM
authors.lastname: Leong
authors.forename: Scott B
authors.initials: SB
authors.lastname: Snapper
mesh_terms: D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins; D054308:Enteropathogenic Escherichia coli / Q000378:metabolism / Q000472:pathogenicity*; D005347:Fibroblasts; D051379:Mice; D018345:Mice, Knockout; D015513:Oncogene Proteins / Q000378:metabolism; D014616:Vaccinia virus / Q000378:metabolism / Q000472:pathogenicity*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C078332:Nck protein; D015513:Oncogene Proteins; C495772:Wasl protein, mouse; C491671:Waspip protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal