Phagosome maturation: aging gracefully

Vieira, Otília V.; Botelho, Roberto J.; Grinstein, Sergio

doi:10.1042/bj20020691

Cited by 614 publications

(629 citation statements)

References 229 publications

(291 reference statements)

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“…A microtubule dependent mechanism is responsible for the rapid relocation of phagosomes from the apical processes back to the base of the cell (Herman and Steinberg 1982). This microtubule dependent transport is not seen in shaker-1mice, however, as before transport can occur the ROS containing phagosomes must first sequentially fuse with apically located endosomes, lysosomes, and melanosomes (reviewed in Vieira et al 2002;Bosch et al 1993). Therefore, as a result of melanosome and lysosome mispositioning, there is also mispositioning of phagosomes resulting in an apparent delay in ROS digestion.…”

Section: Discussionmentioning

confidence: 99%

“…Following its daily burst of ROS phagocytosis, a rapid digestion of the internalized ROS takes place. This process is initiated by the sequential fusion of endosomes, lysosomes, and melanosomes with the ROS containing phagosomes, creating the so-called phagolysosome (reviewed in Vieira et al 2002). Actin may facilitate fusion between endocytic compartments and existing phagosomes, as judged by studies that depolymerize actin (Jahraus et al 2001).…”

Section: Introductionmentioning

confidence: 99%

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The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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Mutations in the myosin-VIIa (MYO7a) gene cause human Usher disease, characterized by hearing impairment and progressive retinal degeneration. In the retina, myosin-VIIa is highly expressed in the retinal pigment epithelium, where it plays a role in the positioning of melanosomes and other digestion organelles. Using a human cultured retinal pigmented epithelia cell line, ARPE-19, as a model system, we have found that a population of myosin-VIIa is associated with cathepsin D-and Rab7-positive lysosomes. Association of myosin-VIIa with lysosomes was Rab7 independent, as dominant negative and dominant active versions of Rab7 did not disrupt myosin-VIIa recruitment to lysosomes. Association of myosin-VIIa with lysosomes was also independent of the actin and microtubule cytoskeleton. Myosin-VIIa copurified with lysosomes on density gradients, and fractionation and extraction experiments suggested that it was tightly associated with the lysosome surface. These studies suggest that myosin-VIIa is a lysosome motor.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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“…Interestingly, CD16-mediated phagocytosis readily induces the oxidative burst response, in contrast to phagocytosis through CR3 (Payne and Horwitz, 1987;Wright and Silverstein, 1983;Lowell, 2006). In this respect, studies in macrophages have shown that CD16-derived phagosomes fuse more readily with lysosomes than CR3-derived phagosomes, suggesting association of CD16 with enhanced microbial killing (Vieira et al, 2002). It seems possible, therefore, that CR3-mediated internalization of P. gingivalis may stay intact with aging, whereas alternative uptake of the pathogen by strongly microbicidal pathways may decline.…”

Section: In Vivo Evidence For Cr3 Exploitation By P Gingivalis and Imentioning

confidence: 99%

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

Hajishengallis

Wang²,

Liang³

et al. 2008

Advances in Experimental Medicine and Biology

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The capacity of certain pathogens to exploit innate immune receptors enables them to undermine immune clearance and persist in their host, often causing disease. Here we review subversive interactions of Porphyromonas gingivalis, a major periodontal pathogen, with the complement receptor-3 (CR3; CD11b/CD18) in monocytes/macrophages. Through its cell surface fimbriae, P. gingivalis stimulates Toll-like receptor-2 (TLR2) inside-out signaling which induces the highaffinity conformation of CR3. Although this activates CR3-dependent monocyte adhesion and transendothelial migration, P. gingivalis has co-opted this TLR2 proadhesive pathway for CR3 binding and intracellular entry. In CR3-deficient macrophages, the internalization of P. gingivalis is reduced 2-fold but its ability to survive intracellularly is reduced 1000-fold, indicating that CR3 is exploited by the pathogen as a relatively safe portal of entry. The interaction of P. gingivalis fimbriae with CR3 additionally inhibits production of bioactive (p70) interleukin-12, which mediates immune clearance. In vivo blockade of CR3 leads to reduced persistence of P. gingivalis in the mouse host and diminished ability to cause periodontal bone loss, the hallmark of periodontal disease. Strikingly, the ability of P. gingivalis to interact with and exploit CR3 depends upon quantitatively minor components (FimCDE) of its fimbrial structure, which predominantly consists of polymerized fimbrillin (FimA). Indeed, isogenic mutants lacking FimCDE but expressing FimA are dramatically less persistent and virulent than the wild-type organism both in vitro and in vivo. This model of immune evasion through CR3 exploitation by P. gingivalis supports the concept that pathogens evolved to manipulate innate immune function for promoting their adaptive fitness.

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“…La membrana de los fagosomas recién formados es similar a la plasmática y su contenido, a los fluidos del espacio extracelular (11). Para degradar las partículas ingeridas, estos fagosomas deben madurar hacia compartimientos ácidos e hidrolíticos.…”

Section: Maduración De Fagosomasunclassified

“…Desde estos fagosomas tempranos se da una recirculación de proteínas a la membrana plasmática que se hace por medio de endosomas de reciclaje, que son molecular y bioquímicamente diferentes a los endosomas tempranos, son menos ácidos (pH ∼6,5) y se caracterizan por la presencia de Rab11 (11).…”

Section: Maduración De Fagosomasunclassified

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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Phagosome maturation: aging gracefully

Cited by 614 publications

References 229 publications

The unconventional myosin-VIIa associates with lysosomes

The unconventional myosin-VIIa associates with lysosomes

Subversion of Innate Immunity by Periodontopathic Bacteria via Exploitation of Complement Receptor-3

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

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