SKIP, the Host Target of the Salmonella Virulence Factor SifA, Promotes Kinesin-1-Dependent Vacuolar Membrane Exchanges

Dumont, Audrey; Boucrot, Emmanuel; Drevensek, Stéphanie; Daire, Vanessa; Gorvel, Jean‐Pierre; Poüs, Christian; Holden, David W.; Méresse, Stéphane

doi:10.1111/j.1600-0854.2010.01069.x

Cited by 103 publications

(129 citation statements)

References 52 publications

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“…Very recently, we identified SKIP/PLEKHM2 (SifA and kinesin-interacting protein) (Boucrot et al, 2005) as a specific GTP-Rab1A-binding protein . As its name indicates, SKIP directly interacts with the kinesin-1 motor (Boucrot et al, 2005;Dumont et al, 2010), and the SKIP-kinesin-1 complex regulates transport of lysosomes to the cell periphery in HeLa cells via an interaction between the RUN domain of SKIP and the GTP-bound form of Arl8 (Arf-like small GTPase) (Rosa-Ferreira and Munro, 2011). Since Rab1A also interacts with the RUN domain of SKIP and melanosomes are lysosome-related organelles, it is highly possible that the Rab1A-SKIP-kinesin-1 complex transports melanosomes to the cell periphery in melanocytes (schematic model is shown in supplementary material Fig.…”

Section: Discussionmentioning

confidence: 99%

Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes

Ishida

Ohbayashi

Maruta

et al. 2012

Journal of Cell Science

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SummaryMelanosomes are transported to the cell periphery of melanocytes by coordination between bidirectional microtubule-dependent movements and unidirectional actin-dependent movement. Although both the mechanism of the actin-dependent melanosome transport and the mechanism of the microtubule-dependent retrograde melanosome transport in mammalian skin melanocytes have already been determined, almost nothing is known about the mechanism of the microtubule-dependent anterograde melanosome transport. Small GTPase Rab proteins are common regulators of membrane traffic in all eukaryotes, and in this study we performed genome-wide screening for Rab proteins that are involved in anterograde melanosome transport by expressing 60 different constitutive active (and negative) mutants, and succeeded in identifying Rab1A, originally described as a Golgi-resident Rab, as a prime candidate. Endogenous Rab1A protein was found to be localized to mature melanosomes in melanocytes, and its functional ablation either by siRNA-mediated knockdown or by overexpression of a cytosolic form of Rab1A-GTPase-activating protein/TBC1D20 induced perinuclear melanosome aggregation. The results of time-lapse imaging further revealed that long-range anterograde melanosome movements were specifically suppressed in Rab1A-deficient melanocytes, whereas retrograde melanosome transport occurred normally. Taken together, these findings indicate that Rab1A is the first crucial component of the anterograde melanosome transport machinery to be identified in mammalian skin melanocytes.

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Section: Discussionmentioning

confidence: 99%

Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes

Ishida

Ohbayashi

Maruta

et al. 2012

Journal of Cell Science

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“…Mammalian proteins SKIP and RhoA form a protein complex with Salmonella effectors SifA and SseJ that promotes host membrane tubulation [212]. In addition, the SifA-SKIP complex plays an essential role in the formation and/or the anterograde movement of PipB2/kinesin-1-positive vesicles that are likely to derive from SCV [213].…”

Section: 5mentioning

confidence: 99%

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Ramos‐Morales

2012

ISRN Cell Biology

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Type III secretion systems are molecular machines used by many Gram-negative bacterial pathogens to inject proteins, known as effectors, directly into eukaryotic host cells. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen's advantage. Salmonella enterica possesses two virulence-related type III secretion systems that deliver more than forty effectors. This paper reviews our current knowledge about the functions, biochemical activities, host targets, and impact on host cells of these effectors. First, the concerted action of effectors at the cellular level in relevant aspects of the interaction between Salmonella and its hosts is analyzed. Then, particular issues that will drive research in the field in the near future are discussed. Finally, detailed information about each individual effector is provided.

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“…For example, the Salmonella enterica SopD2 effector inactivates Rab7, preventing its interactions with RILP and FYCO1 and thus disrupting transport of lysosomes (D'Costa et al, 2015). Another Salmonella effector, SifA, engages SKIP and kinesin-1 to pinch off vesicles from the Salmonella vacuole and move them in anterograde direction (Dumont et al, 2010). SifA also forms a complex with SKIP and Rab9A, preventing transport of mannose 6-phosphate receptors (MPRs) from endosomes to the TGN and thus causing lysosomal dysfunction (McGourty et al, 2012).…”

Section: Immunitymentioning

confidence: 99%

Mechanisms and functions of lysosome positioning

Guardia

Keren-Kaplan

et al. 2016

Journal of Cell Science

461

466

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Lysosomes have been classically considered terminal degradative organelles, but in recent years they have been found to participate in many other cellular processes, including killing of intracellular pathogens, antigen presentation, plasma membrane repair, cell adhesion and migration, tumor invasion and metastasis, apoptotic cell death, metabolic signaling and gene regulation. In addition, lysosome dysfunction has been shown to underlie not only rare lysosome storage disorders but also more common diseases, such as cancer and neurodegeneration. The involvement of lysosomes in most of these processes is now known to depend on the ability of lysosomes to move throughout the cytoplasm. Here, we review recent findings on the mechanisms that mediate the motility and positioning of lysosomes, and the importance of lysosome dynamics for cell physiology and pathology.

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SKIP, the Host Target of the Salmonella Virulence Factor SifA, Promotes Kinesin-1-Dependent Vacuolar Membrane Exchanges

Cited by 103 publications

References 52 publications

Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes

Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes

Impact ofSalmonella entericaType III Secretion System Effectors on the Eukaryotic Host Cell

Mechanisms and functions of lysosome positioning

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