[
International Worm Meeting,
2009]
Semaphorins regulate a wide range of developmental events. In C. elegans, the signal controls morphogenesis of epidermal cells, as shown by the finding that semaphorin mutants display aberrant arrangement of epidermis-derived tissues, rays. To gain insight into semaphorin signaling, we conducted a screen and isolated a loss-of-function mutation in Rictor, which suppressed the ray phenotype in semaphorin mutants. Rictor is known to make a complex TORC2 with TOR. Independently of TORC2, TOR also makes a complex TORC1 with Raptor. Signaling via TORC1 promotes mRNA translation, whereas TORC2 stabilizes F-actin formation. Consistently with previous reports on an antagonistic relationship between two TORC pathways, we found that Raptor overexpression, similarly to Rictor deficiency, suppressed the ray phenotype in semaphorin mutants. Conversely, TORC1 inhibition and TORC2 activation phenocopied semaphorin mutants. Thus, our data indicate that TORC1 cooperates while TORC2 antagonizes with semaphorin signaling. In addition, knockdown of 4EBP, which is a TORC1 substrate and a translation repressor, suppressed the semaphorin mutant phenotype, suggesting that TORC1 mediates the signal by repressing 4EBP and thus activating translation. Likewise, deficiency of PKCa, which is a TORC2 substrate, also suppressed the mutant phenotype, implicating that TORC2 inhibition, which probably results in actin destabilization, also mediates the signal. Therefore, our data imply that TOR serves to integrate the semaphorin input and subsequently transduce it into divergent downstream cascades.