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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
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04 Jun 2010
Olivia Steele-Mortimer
F1000 Microbiology
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, NIH, Hamilton , MT, USA.
F1000 Microbiology
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, NIH, Hamilton , MT, USA.
Carrie Jolly
F1000 Microbiology
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, NIH, Hamilton, MT, USA.
F1000 Microbiology
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, NIH, Hamilton, MT, USA.
New Finding
DOI: 10.3410/f.3489956.3180059
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.
Disclosures
None declared
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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, 19 Jun 2013; F1000Prime.com/3489956
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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.
DOI: 10.1111/j.1600-0854.2010.01069.x
PMID: 20406420
