TY - JOUR
T1 - Ait1 regulates TORC1 signaling and localization in budding yeast
AU - Wallace, Ryan L.
AU - Lu, Eric
AU - Luo, Xiangxia
AU - Capaldi, Andrew P.
N1 - Funding Information:
We thank Claudio De Virgilio for sharing GTR1 and 2 mutant plasmids, and Kyle Cunningham for sharing the GFP-Pib2 plasmid, used to make mutant strains. We also thank Phil Gafken and Lisa Jones of the Fred Hutchinson Cancer Research Center’s Proteomics Facility, and Paul Langlais at the University of Arizona for carrying out the peptide mapping experiments. This work was supported by the National Institutes of Health (NIH) grants R01GM097329 and T32GM136536.
Publisher Copyright:
© 2022, eLife Sciences Publications Ltd. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - 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 Saccharomy-cetaceae/codaceae, and likely other simple eukaryotes, has undergone significant rewiring during evolution.
AB - 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 Saccharomy-cetaceae/codaceae, and likely other simple eukaryotes, has undergone significant rewiring during evolution.
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U2 - 10.7554/eLife.68773
DO - 10.7554/eLife.68773
M3 - Article
C2 - 36047762
AN - SCOPUS:85138491667
SN - 2050-084X
VL - 11
JO - eLife
JF - eLife
M1 - e68773
ER -