SKIP,the Host Target of the Salmonella Virulence Factor SifA,Promotes Kinesin‐1‐Dependent Vacuolar Membrane Exchanges |
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Authors: | Audrey Dumont Emmanuel Boucrot Stéphanie Drevensek Vanessa Daire Jean‐Pierre Gorvel Christian Poüs David W. Holden Stéphane Méresse |
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Affiliation: | 1. 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;2. Centre for Molecular Microbiology and Infection, Imperial College London, Armstrong Road, London SW7 2AZ, UK;3. Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK;4. Université Paris‐Sud, JE2493, IFR141, Faculté de Pharmacie Chatenay‐Malabry, France;5. AP‐HP, H?pital Antoine Béclère, Clamart, France |
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Abstract: | 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. |
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Keywords: | kinesin‐1 microtubule
Salmonella
SifA SKIP |
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