Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

Brumell, John H.; Scidmore, Marci A.

doi:10.1128/mmbr.00023-07

Cited by 189 publications

(206 citation statements)

References 211 publications

(302 reference statements)

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“…A subset of these are Rab GTPases including Rabs 4, 11, and 14, which are associated with recycling endosomes, and Rabs 1, 6, and 10, which are associated with ER-Golgi traffic (Rzomp et al 2006;Brumell and Scidmore 2007;Moorhead et al 2007Moorhead et al , 2010Capmany and Damiani 2010). Rabs 6 and 10 are recruited to inclusions in a species-specific manner, whereas recruitment of Rab1, 4, and 11 appear to be ubiquitous to all Chlamydiae (Rzomp et al 2003).…”

Section: Interactions With Regulators Of Membranetrafficking Pathwaysmentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

206

197

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Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the causative agent of blinding trachoma. Although Chlamydia is protected from humoral immune responses by residing within remodeled intracellular vacuoles, it still must contend with multilayered intracellular innate immune defenses deployed by its host while scavenging for nutrients. Here we provide an overview of Chlamydia biology and highlight recent findings detailing how this vacuole-bound pathogen manipulates host -cellular functions to invade host cells and maintain a replicative niche.

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Section: Interactions With Regulators Of Membranetrafficking Pathwaysmentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

206

197

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“…They act through the GTP-dependent recruitment of protein ligands at the appropriate time and place. Rabs and their effectors localize to vacuoles of intracellular pathogens and are important in phagosome trafficking and maintenance (13). The mature SCV interacts with the late endosomal Rabs, Rab7 and Rab9 (13,15,16).…”

mentioning

confidence: 99%

“…13). Rabs have been implicated in the regulation of all steps of endocytic trafficking in uninfected cells, including vesicle formation, intracellular transport (including binding to motor proteins or motor adaptors), vesicle tethering, and vesicle fusion (reviewed in ref.…”

mentioning

confidence: 99%

The Salmonella virulence protein SifA is a G protein antagonist

Jackson

Nawabi

Hentea

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Salmonella's success at proliferating intracellularly and causing disease depends on the translocation of a major virulence protein, SifA, into the host cell. SifA recruits membranes enriched in lysosome associated membrane protein 1 (LAMP1) and is needed for growth of Salmonella induced filaments (Sifs) and the Salmonella containing vacuole (SCV). It directly binds a host protein called SKIP (SifA and kinesin interacting protein) which is critical for membrane stability and motor dynamics at the SCV. SifA also contains a WxxxE motif, predictive of G protein mimicry in bacterial effectors, but whether and how it mimics the action of a host G protein is not known. We show that SKIP's pleckstrin homology domain, which directly binds SifA, also binds to the late endosomal GTPase Rab9. Knockdown studies suggest that both SKIP and Rab9 function to maintain peripheral LAMP1 distribution in cells. The Rab9:SKIP interaction is GTP-dependent and is inhibited by SifA binding to the SKIP pleckstrin homology domain, suggesting that SifA may be a Rab9 antagonist. SifA:SKIP binding is significantly tighter than Rab9:SKIP binding and may thus allow SifA to bring SKIP to the SCV via SKIP's Rab9-binding site. Rab9 can measurably reverse SifA-dependent LAMP1 recruitment and the perinuclear location of the SCV in cells. Importantly, binding to SKIP requires SifA residues W197 and E201 of the conserved WxxxE signature sequence, leading to the speculation that bacterial G protein mimicry may result in G protein antagonism.GTPase ͉ LAMP1 ͉ Rab9 ͉ SKIP ͉ lysosome

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“…tuberculosis puede alterar el ciclo de reclutamiento y activación de las Rab por los fagosomas, lo que explica en parte la inhibición de la maduración de los fagosomas micobacterianos (46). Se han reportado, principalmente, alteraciones de Rab5 y Rab7, pero también de otras como Rab4, Rab9, Rab11, Rab14 y Rab22a, que a continuación se explicarán en detalle.…”

Section: Alteraciones De La Expresión Y Activación De Las Rab Duranteunclassified

Alteraciones en el reclutamiento y activación de proteínas Rab durante la infección micobacteriana

Castaño

Rojas

2010

biomedica

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En el fagosoma, Mycobacterium spp. altera la activación y reclutamiento de diferentes proteínas "del gen Ras de cerebro de rata", comúnmente conocidas como Rab. En este manuscrito se revisa una serie de reportes que han demostrado que los fagosomas que contienen micobacterias tienen una expresión mayor y sostenida de Rab5, Rab11, Rab14 y Rab22a, y menor o ninguna expresión de Rab7, Rab9 y Rab6. Esto se correlaciona con aumento de la fusión de estos fagosomas con endosomas tempranos y de reciclaje, lo que les permite mantener ciertas características de compartimentos tempranos, permite que las bacterias obtengan acceso a nutrientes y previene la activación de mecanismos contra la micobacteria. La expresión de mutantes constitutivamente activos de las Rab de endosomas tempranos impide la maduración de fagosomas que contienen esferas de látex o micobacterias inactivadas por calor. Mientras que su silenciamiento, mediante ARN de interferencia o mediante dominantes negativos, induce la maduración de fagosomas micobacterianos. Los mecanismos exactos por los que las micobacterias alteran la dinámica de expresión de estas GTPasas, afectando la maduración fagolisosómica, no se han establecido. El problema podría explicarse por defectos en el reclutamiento de las proteínas que interactúan con Rab, como la cinasa-3 del fosfatidilinositol y el antígeno endosómico temprano 1. La identificación de los mecanismos empleados por Mycobacterium spp. para interrumpir el ciclo de activación de las Rab, será esencial para comprender la fisiopatología de la infección micobacteriana y útil como posibles blancos farmacológicos.Palabras clave: tuberculosis, Mycobacterium tuberculosis, proteínas de unión a GTP rab, proteínas SNARE, fagosomas, endosomas. Alterations in recruitment and activation of Rab proteins during mycobacterial infectionAt the phagosome level, Mycobacterium spp. alters activation and recruitment of several "Ras gene from rat brain" proteins, commonly known as Rab. Mycobacterial phagosomes have a greater and sustained expression of Rab5, Rab11, Rab14 and Rab22a, and lowered or no expression of Rab7, Rab9 and Rab6. This correlates with increased fusion of the phagosomes with early and recycling endosomes acquiring some features of early phogosomes, allowing the bacteria to gain access to nutrients and preventing the activation of anti-mycobacterial mechanisms. The expression of constitutively active mutants of Rab from the early stage endosomes prevents the maturation of phagosomes containing latex beads or heat-inactivated mycobacteria. Silencing of these mutants by interference RNA or dominant negative forms induces the maturation of mycobacterial phagosomes. The mechanisms have not been established by which mycobacteria alter the expression of these GTPases and thereby shift the phagolysosomal maturation. The problem can be explained by alterations in the recruitment of proteins that interact with Rab, such as phosphoinositide 3-kinases and early endosomal antigen 1. Identifying the mechanisms used by Mycobacterium sp...

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Manipulation of Rab GTPase Function by Intracellular Bacterial Pathogens

Cited by 189 publications

References 211 publications

Chlamydial Intracellular Survival Strategies

Chlamydial Intracellular Survival Strategies

The Salmonella virulence protein SifA is a G protein antagonist

Alteraciones en el reclutamiento y activación de proteínas Rab durante la infección micobacteriana

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