Ait1 regulates TORC1 signaling and localization in budding yeast

  1. Ryan L Wallace
  2. Eric Lu
  3. Xiangxia Luo
  4. Andrew P Capaldi  Is a corresponding author
  1. University of Arizona, United States

Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Ryan L Wallace

    Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Eric Lu

    Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3144-3563
  3. Xiangxia Luo

    Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrew P Capaldi

    Department of Molecular and Cellular Biology, University of Arizona, Tucson, United States
    For correspondence
    capaldi@email.arizona.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7902-2477

Funding

National Institute of General Medical Sciences (R01GM097329)

  • Andrew P Capaldi

National Institute of General Medical Sciences (T32GM136536)

  • Ryan L Wallace
  • Andrew P Capaldi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Roger J Davis, University of Massachusetts Medical School, United States

Version history

  1. Received: March 25, 2021
  2. Accepted: August 31, 2022
  3. Accepted Manuscript published: September 1, 2022 (version 1)
  4. Version of Record published: September 22, 2022 (version 2)

Copyright

© 2022, Wallace et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ryan L Wallace
  2. Eric Lu
  3. Xiangxia Luo
  4. Andrew P Capaldi
(2022)
Ait1 regulates TORC1 signaling and localization in budding yeast
eLife 11:e68773.
https://doi.org/10.7554/eLife.68773

Share this article

https://doi.org/10.7554/eLife.68773

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