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    J Cell Biol. 2006 Jun 19;173(6):963-74.

    TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth.

    Hennig KM, Colombani J, Neufeld TP.

    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.

    Target of rapamycin (TOR) is a central regulator of cellular and organismal growth in response to nutrient conditions. In a genetic screen for novel TOR interactors in Drosophila melanogaster, we have identified the clathrin-uncoating ATPase Hsc70-4, which is a key regulator of endocytosis. We present genetic evidence that TOR signaling stimulates bulk endocytic uptake and inhibits the targeted endocytic degradation of the amino acid importer Slimfast. Thus, TOR simultaneously down-regulates aspects of endocytosis that inhibit growth and up-regulates potential growth-promoting functions of endocytosis. In addition, we find that disruption of endocytosis leads to changes in TOR and phosphatidylinositol-3 kinase activity, affecting cell growth, autophagy, and rapamycin sensitivity. Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling.

    PMID: 16785324 [PubMed - indexed for MEDLINE]

    PMCID: 1950482

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