Target genes of insulin and TOR signaling in Drosophila

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Proper regulation of cell growth and division is critical for development of all metazoans. Whereas much is known about the mechanics of cell cycle progression and the signals that control this process in a unicellular context, much less is known on how different tissues and organ systems of multicellular organisms interact to coordinate their growth. A crucial factor in determining cell and organismal growth is nutrient availability, and the current proposal focuses on the regulatory function of amino acids in growth control during Drosophila larval development. Although it is well recognized that protein intake is a dominant factor in animal growth, the mechanism by which information on amino acid availability is sensed and propagated throughout the body is unknown. For example, a molecule which may perform analogous function as insulin for glucose, or leptin for fat, has not been identified for amino acids. Recent studies in yeasts and mammalian cells have shown that signaling by TOR (target of rapamycin), which has homology to phosphatidylinositol kinases, controls translation initiation and cell cycle progression in response to nutrients, including amino acids. TOR was initially identified as an intracellular target of rapamycin, an immunosuppressant which blocks proliferation of T cells. Although TOR has not yet been identified in Drosophila, evolutionary considerations strongly argue for its presence, and our hypothesis is that amino acids control cell growth through the TOR signaling pathway. To test this, we will investigate the function of TOR proteins in Drosophila.