SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges.
Traffic. 2010 Jul 1; 11(7):899-911
This article is interesting because the authors identified previously unknown functions of the eukaryotic protein, SKIP (SifA and kinesin-interacting protein).
SKIP was originally identified as a eukaryotic protein that interacts with SifA, a Salmonella T3SS-2 effector. Previous studies demonstrated that the SifA/SKIP complex is essential for: 1) maintaining the integrity of the Salmonella-containing vacuole (SCV); 2) formation of endosomal tubules that originate from the SCV during intracellular replication; and 3) virulence in mice. In this study, the authors provide the first evidence of the function of SKIP in eukaryotic cells. They demonstrate that the N-terminal RUN (RPIP8, UNC-14 and NESCA) domain of SKIP (through its interaction with kinesin-1) influences organelle distribution, particularly of the late endosomes/lysosomes and the trans-golgi network. SKIP-induced anterograde movement of these organelles was shown to be dependent on the microtubule network. Also, the authors demonstrate that, in Salmonella-infected host cells, the SifA/SKIP complex is necessary for the formation and/or transport of PipB2-and kinesin-1 vesicles that bud from the SCV. This study brings us one step closer to understanding how Salmonella manipulate the host cell trafficking pathways during intracellular replication.
Steele-Mortimer O and Jolly C: F1000Prime Recommendation of [Dumont A et al., Traffic 2010, 11(7):899-911]. In F1000Prime, 04 Jun 2010; DOI: 10.3410/f.3489956.3180059. F1000Prime.com/3489956#eval3180059
F1000Prime Recommendations, Dissents and Comments for [Dumont A et al., Traffic 2010, 11(7):899-911]. In F1000Prime, 10 Dec 2013; F1000Prime.com/3489956
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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