Extended Data Figure 10: SZT2–GATOR–SESN2 in nutrient sensing and mTORC1 signalling.

We propose that the SZT2-orchestrated GATOR (SOG) complex sets a platform for nutrient sensing and mTORC1 regulation in metazoans. In this model, GATOR1 not only functions as a GAP that inactivates RAGA and RAGB (not depicted), but also recruits GATOR2 to the lysosome through SZT2. Under nutrient-deprived conditions, SESN2 is further recruited to the lysosome, and represses RAGA/B through its GDI activity. Upon nutrient stimulation, the GAP activity of GATOR1 may be repressed by GATOR2 through unknown mechanisms, whereas the leucine-bound SESN2 dissociates from GATOR2. In line with the general mode of GDI regulation, leucine could be considered as a GDI-dissociation factor (GDF) for SESN2. In SZT2-deficient cells, GATOR1, GATOR2 and probably SESN2 dissociate from the lysosome resulting in constitutive RAGA/B activation and mTORC1 signalling, but the leucine-regulated SESN2 interaction with GATOR2 is not affected. a.a., amino acids; Leu, leucine.