Figure 1.

Two potential mechanisms of mTORC1 regulation by SESTRINs via GATOR and RRAG-A/(B) proteins. SESTRINs interact with GATOR and RRAGs and regulate mTORC1 activity via a RRAG-dependent mechanism. Two models can explain the regulation of RRAG-A/B activity by SESTRINs. In model (A), SESTRINs interact directly but weakly with RRAG-A/B. GATOR2, being a strong interactor for SESTRIN2, stabilizes interactions between SESTRINs and RRAGs, thus supporting the inhibitory effects of SESTRINs on RRAG-A/B. In model (B), interactions between SESTRINs and RRAGs are solely mediated by GATOR, which transmits an inhibitory signal from SESTRINs toward RRAG-A/B.