Ait1 regulates TORC1 signaling and localization in budding yeast

The target of rapamycin complex I (TORC1) regulates cell growth and metabolism in eukaryotes. Previous studies have shown that nitrogen and amino acid signals activate TORC1 via the highly conserved small GTPases, Gtr1/2 (RagA/C in humans), and the GTPase activating complex SEAC/GATOR. However, it remains unclear if, and how, other proteins/pathways regulate TORC1 in simple eukaryotes like yeast. Here, we report that the previously unstudied GPCR-like protein, Ait1, binds to TORC1-Gtr1/2 in Saccharomyces cerevisiae and holds TORC1 around the vacuole during log-phase growth. Then, during amino acid starvation, Ait1 inhibits TORC1 via Gtr1/2 using a loop that resembles the RagA/C-binding domain in the human protein SLC38A9. Importantly, Ait1 is only found in the Saccharomycetaceae/codaceae, two closely related families of yeast that have lost the ancient TORC1 regulators Rheb and TSC1/2. Thus, the TORC1 circuit found in the Saccharomycetaceae/codaceae, and likely other simple eukaryotes, has undergone significant rewiring during evolution.

Automated summary

Previous studies have identified mechanisms by which TORC1 is activated by nitrogen and amino acid signals, but it is still unclear how other proteins/pathways regulate TORC1 in simple eukaryotes like yeast. This study discovered a previously uncharacterized GPCR-like protein, Ait1, which binds to TORC1-Gtr1/2 in yeast and regulates TORC1 activity. Under amino acid starvation, Ait1 inhibits TORC1 activity by interacting with Gtr1/2, similar to how the human protein SLC38A9 interacts with RagA/C.