IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation.
IRSp53 links the enterohemorrhagic E. coli effectors Tir and EspFU for actin pedestal formation.
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DOI：
10.1016/j.chom.2009.02.003
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发表时间：
2009-03
影响因子：
30.3
通讯作者：
Stefanie M. Weiss;Markus Ladwein;D. Schmidt;Julia Ehinger;S. Lommel;K. Städing;U. Beutling;Andrea Disanza;R. Frank;L. Jänsch;G. Scita;F. Gunzer;K. Rottner;T. Stradal
中科院分区：
文献类型：
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作者：
Stefanie M. Weiss;Markus Ladwein;D. Schmidt;Julia Ehinger;S. Lommel;K. Städing;U. Beutling;Andrea Disanza;R. Frank;L. Jänsch;G. Scita;F. Gunzer;K. Rottner;T. Stradal
肌动蛋白基底形成的病因。大肠杆菌需要细菌内膜素受体Tir的信号传导，其诱导由N-WASP和Arp2/3复合物介导的宿主细胞肌动蛋白聚合。而典型的肠致病性。大肠杆菌（EPEC）通过酪氨酸激酶信号级联，肠出血招募这些肌动蛋白调节因子。大肠杆菌（EHEC） O157:H7使用细菌效应物EspFU(TccP)，一种有效的N-WASP激活剂。在这里，我们发现IRSp53家族成员，膜和肌动蛋白动力学的关键调节因子，直接与Tir和EspFU相互作用。IRSp53与espfund和N-WASP在肌动蛋白基座上共定位。此外，IRSp53的靶向与espfu和N-WASP无关，但需要Tir残基454-463，这是先前证明的espfu依赖性肌动蛋白组装所必需的。IRSp53的遗传和功能缺失会破坏肠出血性大肠杆菌介导的肌动蛋白组装。总的来说，这些数据确定了IRSp53家族蛋白是连接细菌Tir和EspFUin EHEC基座形成的缺失宿主细胞因子。
Actin pedestal formation by pathogenicE. colirequires signaling by the bacterial intimin receptor Tir, which induces host cell actin polymerization mediated by N-WASP and the Arp2/3 complex. Whereas canonical enteropathogenicE. coli(EPEC) recruit these actin regulators through tyrosine kinase signaling cascades, enterohemorrhagicE. coli(EHEC) O157:H7 employ the bacterial effector EspFU(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 EspFU. IRSp53 colocalizes with EspFUand N-WASP in actin pedestals. In addition, targeting of IRSp53 is independent of EspFUand N-WASP but requires Tir residues 454–463, previously shown to be essential for EspFU-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 EspFUin EHEC pedestal formation.