Centre d'Immunologie de Marseille-Luminy, CNRS UMR 6102, INSERM U631, Université de la Méditerranée, Parc Scientifique de Luminy, Case 906-13288 Marseille Cedex 9, France.
Traffic. 2010 Jul 1;11(7):899-911. doi: 10.1111/j.1600-0854.2010.01069.x. Epub 2010 Apr 6.
In Salmonella-infected cells, the bacterial effector SifA forms a functional complex with the eukaryotic protein SKIP (SifA and kinesin-interacting protein). The lack of either partner has important consequences on the intracellular fate and on the virulence of this pathogen. In addition to SifA, SKIP binds the microtubule-based motor kinesin-1. Yet the absence of SifA or SKIP results in an unusual accumulation of kinesin-1 on the bacterial vacuolar membrane. To understand this apparent contradiction, we investigated the interaction between SKIP and kinesin-1 and the function of this complex. We show that the C-terminal RUN (RPIP8, UNC-14 and NESCA) domain of SKIP interacted specifically with the tetratricopeptide repeat (TPR) domain of the kinesin light chain. Overexpression of SKIP induced a microtubule- and kinesin-1-dependent anterograde movement of late endosomal/lysosomal compartments. In infected cells, SifA contributed to the fission of vesicles from the bacterial vacuole and the SifA/SKIP complex was required for the formation and/or the anterograde transport of kinesin-1-enriched vesicles. These observations reflect the role of SKIP as a linker and/or an activator for kinesin-1.
在沙门氏菌感染的细胞中，细菌效应蛋白 SifA 与真核蛋白 SKIP（SifA 和驱动蛋白相互作用蛋白）形成功能复合物。任一伙伴的缺失都会对病原体的细胞内命运和毒力产生重要影响。除了 SifA，SKIP 还结合基于微管的运动蛋白驱动蛋白-1。然而，SifA 或 SKIP 的缺失会导致驱动蛋白-1在细菌液泡膜上异常积聚。为了理解这一明显的矛盾，我们研究了 SKIP 和驱动蛋白-1之间的相互作用以及该复合物的功能。我们表明，SKIP 的 C 端 RUN（RPIP8、UNC-14 和 NESCA）结构域与驱动蛋白轻链的四肽重复（TPR）结构域特异性相互作用。SKIP 的过表达诱导晚期内体/溶酶体区室的微管和驱动蛋白-1依赖性顺行运动。在感染细胞中，SifA 有助于从细菌液泡中分离小泡，并且 SifA/SKIP 复合物对于富含驱动蛋白-1的小泡的形成和/或顺行运输是必需的。这些观察结果反映了 SKIP 作为驱动蛋白-1的连接子和/或激活剂的作用。
