The target of rapamycin (TOR) is a well-known cell growth regulator conserved from yeast to mammals. TOR pathway regulates a variety of processes contributing to cell growth, autophagy and actin polymerization. TOR forms two distinct multiprotein complexes, TORC1 and 2. The TORC1 consists of TOR, LST8 and Raptor, and phosphorylates S6K and 4E-BP, regulating cell growth. Inactivation of TORC1 induces autophagy despite the presence of proper nutrients. TORC2 contains TOR, LST8, SIN1 and Rictor. TORC2 signals to actin cytoskeleton by activating Rho1 GTPase switch. TORC2 also phosphorylates and activates Akt. The role of Akt includes regulation of cell proliferation and survival. To determine the in vivo role of Raptor, I have generated and characterized the loss-of-function and the gain-of-function mutants for Raptor. Raptor loss-of-function mutants show developmental defects beyond the second instar larval stage. This result demonstrates that Raptor is required for early developmental processes. Consistently, ectopic expression of Raptor shows inhibited cell growth phenotypes in wings.
TORC1 is reported to control cell growth by activating of S6 kinase (S6K). Therefore, I examined genetic interactions between Raptor and S6K. Knock-down of Raptor using a wing-specific driver generates bent-up wing phenotypes which can be rescued by overexpression of S6K. Moreover, in western blot analyses, I could hardly detect S6K Thr398 phosphorylation in Raptor null mutants. These results demonstrate that Raptor positively regulates S6K activity in Drosophila.