FTY720-induced endocytosis of yeast and human amino acid transporters is preceded by reduction of their inherent activity and TORC1 inhibition.

FTY720 is a sphingoid base analog that acts as an anticancer agent in animal models. Its effect on tumor cells stems largely from its ability to trigger endocytosis of several nutrient transporters. The observation that FTY720 similarly stimulates downregulation of amino acid permeases in yeast suggests that the cellular mechanisms it targets, which are still poorly characterized, are evolutionarily conserved.

The AP-3 adaptor complex mediates sorting of yeast and mammalian PQ-loop-family basic amino acid transporters to the vacuolar/lysosomal membrane.

The limiting membrane of lysosomes in animal cells and that of the vacuole in yeast include a wide variety of transporters, but little is known about how these proteins reach their destination membrane. The mammalian PQLC2 protein catalyzes efflux of basic amino acids from the lysosome, and the similar Ypq1, -2, and -3 proteins of yeast perform an equivalent function at the vacuole. We here show that the Ypq proteins are delivered to the vacuolar membrane via the alkaline phosphatase (ALP) trafficking pathway, which requires the AP-3 adaptor complex.

Tropheryma whipplei, the agent of Whipple's disease, affects the early to late phagosome transition and survives in a Rab5- and Rab7-positive compartment.

Tropheryma whipplei, the agent of Whipple's disease, inhibits phago-lysosome biogenesis to create a suitable niche for its survival and replication in macrophages. To understand the mechanism by which it subverts phagosome maturation, we used biochemical and cell biological approaches to purify and characterise the intracellular compartment where Tropheryma whipplei resides using mouse bone-marrow-derived macrophages. We showed that in addition to Lamp-1, the Tropheryma whipplei phagosome is positive for Rab5 and Rab7, two GTPases required for the early to late phagosome transition.

Tobacco mosaic virus in the lungs of mice following intra-tracheal inoculation.

Plant viruses are generally considered incapable of infecting vertebrates. Accordingly, they are not considered harmful for humans. However, a few studies questioned the certainty of this paradigm.

Impaired stimulation of p38α-MAPK/Vps41-HOPS by LPS from pathogenic Coxiella burnetii prevents trafficking to microbicidal phagolysosomes.

Variations in lipopolysaccharide (LPS), a bacterial outer membrane component, determine virulence of the obligate intracellular bacterium Coxiella burnetii, but the underlying mechanisms are unknown. We find that while avirulent C. burnetii LPS (avLPS) stimulates host p38α-MAPK signaling required for proper trafficking of bacteria containing compartments to lysosomes for destruction, pathogenic C.

Effects of Coxiella burnetii on MAPKinases phosphorylation.

Q fever is a disease caused by Coxiella burnetii, an obligate intracellular bacterium. Acute Q fever is characterized by efficient immune response, whereas chronic Q fever is characterized by dysregulated immune response as demonstrated by the lack of granulomas, the failure of C. burnetii to induce lymphoproliferation, and interferon-γ production.

IL-16 promotes T. whipplei replication by inhibiting phagosome conversion and modulating macrophage activation.

The replication of Tropheryma whipplei (the agent of Whipple's disease) within human macrophages is associated with the expression of IL-16, a cytokine known for its chemotactic and inflammatory properties. In this study, we asked whether IL-16 acts on T. whipplei replication by interfering with the endocytic pathway.

Hijacked phagosomes and leukocyte activation: an intimate relationship.

Intracellular pathogens have developed different strategies to survive within host cells. For example, these pathogens might interfere with the biogenesis of phagolysosomes, thereby forming replicative vacuoles. Although the complex mechanisms used by pathogens to hijack the biogenesis of phagolysosomes have been elucidated in naive leukocytes, the role of leukocyte activation in this process has not yet been investigated.