肠致病性大肠杆菌招募细胞肌醇磷酸酶 SHIP2 来调节肌动蛋白足形成。

Enteropathogenic Escherichia coli recruits the cellular inositol phosphatase SHIP2 to regulate actin-pedestal formation.

机构信息

University of Cambridge, Department of Pathology, Tennis Court Road, Cambridge CB21QP, UK.

出版信息

Cell Host Microbe. 2010 Jan 21;7(1):13-24. doi: 10.1016/j.chom.2009.12.004.

DOI:10.1016/j.chom.2009.12.004

PMID:20114025

Abstract

Adhesion of enteropathogenic Escherichia coli to epithelial cells triggers actin-rich pedestal formation beneath the bacteria. Pedestal formation requires delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane. The C-terminal regions in Tir, encompassing Y483 and Y511, share sequence similarity with cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs), which are critical regulators of eukaryotic signaling pathways. We demonstrate that Y483 and Y511 within tandem ITIM-like sequences are essential for recruiting SHIP2, a host inositol phosphatase. SHIP2 controls condensed F-actin-pedestal formation by engaging the adaptor SHC and by generating a PI(3,4)P(2)-enriched lipid platform for recruitment of the cytoskeletal regulator lamellipodin. Therefore, mimicry of eukaryotic receptor motifs by Tir controls both the lipid and protein composition of the signaling platform necessary for pedestal formation. Further, the dual action of SHIP2's scaffolding and phosphatase functions ensures tight compartmentalization and coordination of actin dynamics during pedestal formation.

摘要

肠致病性大肠杆菌与上皮细胞的黏附会触发细菌下方富含肌动蛋白的足状突起的形成。足状突起的形成需要将细菌易位的紧密素受体（Tir）递送到宿主质膜中并插入其中。Tir 中的 C 末端区域，包含 Y483 和 Y511，与细胞免疫受体酪氨酸抑制基序（ITIM）具有序列相似性，ITIM 是真核信号通路的关键调节因子。我们证明，串联 ITIM 样序列中的 Y483 和 Y511 对于招募 SHIP2（一种宿主肌醇磷酸酶）是必需的。SHIP2 通过结合衔接蛋白 SHC 并生成富含 PI(3,4)P(2)的脂筏平台来募集细胞骨架调节蛋白斑联蛋白，从而控制凝聚的 F-肌动蛋白足状突起的形成。因此，Tir 对真核受体基序的模拟控制了形成足状突起所需的信号转导平台的脂质和蛋白质组成。此外，SHIP2 的支架和磷酸酶功能的双重作用确保了在足状突起形成过程中肌动蛋白动力学的紧密分隔和协调。