Genetic analysis of TOR signaling in Drosophila.

Over a 4-day period of development, Drosophila larvae undergo a roughly 1,000-fold increase in mass. This impressive growth requires a continuous source of dietary protein; in the absence of amino acids, growth is arrested and various larval tissues display characteristic cell-cycle, metabolic, and structural changes. Mutations in the Drosophila target of rapamycin (dTOR) gene result in strikingly similar phenotypes, suggesting that dTOR acts in a signaling pathway responsive to nutrient availability. Genetic epistasis experiments indicate that dTOR is also required for cell growth in response to insulin and PI3K signaling, and that S6K activation can partially rescue dTOR loss of function. Thus dTOR has roles in both nutrient- and growth factor-mediated signaling, and may act to coordinate the activities of these pathways during development. Here we describe the use of mutations in dTOR to dissect its role in various signaling events, to gain insight into TOR protein structure, and to identify novel factors involved in TOR signaling.