title: IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation.
abstract: Actin pedestal formation by pathogenic E. coli requires signaling by the bacterial intimin receptor Tir, which induces host cell actin polymerization mediated by N-WASP and the Arp2/3 complex. Whereas canonical enteropathogenic E. coli (EPEC) recruit these actin regulators through tyrosine kinase signaling cascades, enterohemorrhagic E. coli (EHEC) O157:H7 employ the bacterial effector EspF(U) (TccP), a potent N-WASP activator. Here, we show that IRSp53 family members, key regulators of membrane and actin dynamics, directly interact with both Tir and EspF(U). IRSp53 colocalizes with EspF(U) and N-WASP in actin pedestals. In addition, targeting of IRSp53 is independent of EspF(U) and N-WASP but requires Tir residues 454-463, previously shown to be essential for EspF(U)-dependent actin assembly. Genetic and functional loss of IRSp53 abrogates actin assembly mediated by EHEC. Collectively, these data indentify IRSp53 family proteins as the missing host cell factors linking bacterial Tir and EspF(U) in EHEC pedestal formation.
authors.affiliation: Signalling and Motility Group, Helmholtz Centre for Infection Research, D-38124 Braunschweig, Germany.
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Weiss
authors.forename: Markus
authors.initials: M
authors.lastname: Ladwein
authors.forename: Dorothea
authors.initials: D
authors.lastname: Schmidt
authors.forename: Julia
authors.initials: J
authors.lastname: Ehinger
authors.forename: Silvia
authors.initials: S
authors.lastname: Lommel
authors.forename: Kai
authors.initials: K
authors.lastname: Städing
authors.forename: Ulrike
authors.initials: U
authors.lastname: Beutling
authors.forename: Andrea
authors.initials: A
authors.lastname: Disanza
authors.forename: Ronald
authors.initials: R
authors.lastname: Frank
authors.forename: Lothar
authors.initials: L
authors.lastname: Jänsch
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
authors.forename: Florian
authors.initials: F
authors.lastname: Gunzer
authors.forename: Klemens
authors.initials: K
authors.lastname: Rottner
authors.forename: Theresia E B
authors.initials: TE
authors.lastname: Stradal
mesh_terms: D000199:Actins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D019453:Escherichia coli O157 / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D000199:Actins; C119539:BAIAP2 protein, human; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; C489109:EspFU protein, E coli; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C109287:Tir protein, E coli