A novel type 3 secretion system effector, YspI of Yersinia enterocolitica, induces cell paralysis by reducing total focal adhesion kinase.
A novel type 3 secretion system effector, YspI of Yersinia enterocolitica, induces cell paralysis by reducing total focal adhesion kinase.
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一种新型 3 型分泌系统效应子，小肠结肠炎耶尔森氏菌的 YspI，通过减少总粘着斑激酶来诱导细胞麻痹。
DOI：
10.1111/cmi.12393
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发表时间：
2015
影响因子：
3.4
通讯作者：
Young,GlennM
中科院分区：
文献类型：
--
作者：
LeGrand,Karen;Matsumoto,Hiroyuki;Young,GlennM
一些世界上最重要的疾病是由细菌病原体引起的，这些细菌病原体使用III型分泌系统将毒性效应蛋白直接递送到真核细胞中。由这些病原体引起的无数病理结果部分地由宿主细胞生理学的操纵决定，这是由于每个病原体所采用的独特套件中的单个效应物的特异性活性。YspI被发现是一种效应子，由小肠结肠炎耶尔森氏菌生物变种1B传递，抑制宿主细胞运动。YspI的作用是通过其与粘着斑激酶FAK的特异性相互作用来实现的，FAK是控制细胞运动的粘着斑复合物的支点。这种相互作用是由结合到FAK激酶结构域的YspI的特定结构域定义的。进一步的研究表明，YspI-FAK相互作用导致FAK稳态水平降低，而不改变其磷酸化状态。这些观察和结果表明，YspI通过靶向粘着斑复合物的关键调节因子来抑制细胞运动，从而显示出独特的功能。
Some of the world's most important diseases are caused by bacterial pathogens that deliver toxic effector proteins directly into eukaryotic cells using type III secretion systems. The myriad of pathological outcomes caused by these pathogens is determined, in part, by the manipulation of host cell physiology due to the specific activities of individual effectors among the unique suite each pathogen employs. YspI was found to be an effector, delivered byYersinia enterocoliticaBiovar 1B, that inhibits host cell motility. The action of YspI comes about through its specific interaction with focal adhesion kinase, FAK, which is a fulcrum of focal adhesion complexes for controlling cellular motility. The interaction was defined by a specific domain of YspI that bound to the FAK kinase domain. Further examination revealed that YspI–FAK interaction leads to a reduction of FAK steady‐state levels without altering its phosphorylation state. This collection of observations and results showed YspI displays unique functionality by targeting the key regulator of focal adhesion complexes to inhibit cellular movement.