SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges.
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.
Dumont
Audrey
A
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.
Boucrot
Emmanuel
E
Drevensek
Stéphanie
S
Daire
Vanessa
V
Gorvel
Jean-Pierre
JP
Poüs
Christian
C
Holden
David W
DW
Méresse
Stéphane
S
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D012475:Salmonella / Q000378:metabolism / Q000472:pathogenicity*; D012480:Salmonella Infections / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism* / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D006023:Glycoproteins; C488101:KIF5B protein, human; C466999:SPHKAP protein, human; C421862:SifA protein, Salmonella; D037521:Virulence Factors; D016547:Kinesins