IRSp53 Links the Enterohemorrhagic E-coli Effectors Tir and EspFU for Actin Pedestal Formation

被引：83

作者：

Weiss, Stefanie M. ^{[1
]}

Ladwein, Markus ^{[2
]}

Schmidt, Dorothea ^{[6
]}

Ehinger, Julia ^{[2
]}

Lornmel, Silvia ^{[5
]}

Staeding, Kai ^{[1
]}

Beutling, Ulrike ^{[4
]}

Disanza, Andrea ^{[7
,8
]}

Frank, Ronald ^{[4
]}

Jaensch, Lothar ^{[3
]}

Scita, Giorgio ^{[7
,8
]}

Gunzer, Florian ^{[6
]}

Rottner, Klemens ^{[2
]}

Stradal, Theresia E. B. ^{[1
]}

机构：

[1] Helmholtz Ctr Infect Res, Signalling & Motil Grp, D-38124 Braunschweig, Germany

[2] Helmholtz Ctr Infect Res, Cytoskeleton Dynam Grp, D-38124 Braunschweig, Germany

[3] Helmholtz Ctr Infect Res, Cellular Prote Grp, D-38124 Braunschweig, Germany

[4] Helmholtz Ctr Infect Res, Dept Biol Chem, D-38124 Braunschweig, Germany

[5] Univ Bonn, D-53121 Bonn, Germany

[6] Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Med Microbiol & Hyg, D-01307 Dresden, Germany

[7] Inst FIRC Mol Oncol, IFOM Fdn, I-20139 Milan, Italy

[8] Univ Milan, Sch Med, Dpt San Paolo, I-20139 Milan, Italy

来源：

CELL HOST & MICROBE | 2009年 / 5卷 / 03期

关键词：

ALDRICH-SYNDROME PROTEIN; N-WASP; HOMOLOGY DOMAIN; ALPHA-ACTININ; NCK; MEMBRANE; RECEPTOR; O157-H7; PHOSPHORYLATION; PEPTIDE;

D O I：

10.1016/j.chom.2009.02.003

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：244 / 258

页数：15

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