TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth.
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.
Hennig
Krista M
KM
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Colombani
Julien
J
Neufeld
Thomas P
TP
D026905:Amino Acid Transport Systems / Q000378:metabolism; D000818:Animals; D049108:Cell Enlargement; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D005216:Fat Body / Q000166:cytology*; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011494:Protein Kinases; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
D026905:Amino Acid Transport Systems; D029721:Drosophila Proteins; D050883:HSC70 Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; C424447:Hsc70-4 protein, Drosophila; C478492:slif protein, Drosophila; C416303:target of rapamycin protein, Drosophila