title: Formin-mediated actin polymerization promotes Salmonella invasion.
abstract: Salmonella invade host cells using Type 3 secreted effectors, which modulate host cellular targets to promote actin rearrangements at the cell surface that drive bacterial uptake. The Arp2/3 complex contributes to Salmonella invasion but is not essential, indicating other actin regulatory factors are involved. Here, we show a novel role for FHOD1, a formin family member, in Salmonella invasion. FHOD1 and Arp2/3 occupy distinct microdomains at the invasion site and control distinct aspects of membrane protrusion formation. FHOD1 is phosphorylated during infection and this modification is required for promoting bacterial uptake by host cells. ROCK II, but not ROCK I, is recruited to the invasion site and is required for FHOD1 phosphorylation and for Salmonella invasion. Together, our studies revealan important phospho-dependent FHOD1 actin polymerization pathway in Salmonella invasion.
authors.affiliation: Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada, M5G 1X8; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, M5S 1A8.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Truong
authors.forename: Danielle
authors.initials: D
authors.lastname: Brabant
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bashkurov
authors.forename: Leo C K
authors.initials: LC
authors.lastname: Wan
authors.forename: Virginie
authors.initials: V
authors.lastname: Braun
authors.forename: Won Do
authors.initials: WD
authors.lastname: Heo
authors.forename: Tobias
authors.initials: T
authors.lastname: Meyer
authors.forename: Laurence
authors.initials: L
authors.lastname: Pelletier
authors.forename: John
authors.initials: J
authors.lastname: Copeland
authors.forename: John H
authors.initials: JH
authors.lastname: Brumell
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism*; D000199:Actins; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D058947:Bacterial Secretion Systems; D002460:Cell Line; D005326:Fetal Proteins / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D012480:Salmonella Infections / Q000382:microbiology / Q000635:transmission*; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C103987:SopE protein, Salmonella; D054460:rho-Associated Kinases; C489224:SopB protein, Salmonella