Multilayered regulation of TORC1-body formation in budding yeast

The target of rapamycin kinase complex 1 (TORC1) regulates cell growth and metabolism in eukaryotes. In Saccharomyces cerevisiae, TORC1 activity is known to be controlled by the conserved GTPases, Gtr1/2, and movement into and out of an inactive agglomerate/body. However, it is unclear whether/how these regulatory steps are coupled. Here we show that active Gtr1/2 is a potent inhibitor of TORC1-body formation, but cells missing Gtr1/2 still form TORC1-bodies in a glucose/nitrogen starvation-dependent manner. We also identify 13 new activators of TORC1-body formation and show that seven of these proteins regulate the Gtr1/2-dependent repression of TORC1-body formation, while the remaining proteins drive the subsequent steps in TORC1 agglomeration. Finally, we show that the conserved phosphatidylinositol-3-phosphate (PI(3)P) binding protein, Pib2, forms a complex with TORC1 and overrides the Gtr1/2-dependent repression of TORC1-body formation during starvation. These data provide a unified, systems-level model of TORC1 regulation in yeast.