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Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases

  1. Kim Hou Chia
  2. Tomoyuki Fukuda  Is a corresponding author
  3. Fajar Sofyantoro
  4. Takato Matsuda
  5. Takamitsu Amai
  6. Kazuhiro Shiozaki  Is a corresponding author
  1. Nara Institute of Science and Technology, Japan
Research Article
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Cite this article as: eLife 2017;6:e30880 doi: 10.7554/eLife.30880

Abstract

TOR complex 1 (TORC1) is an evolutionarily conserved protein kinase complex that promotes cellular macromolecular synthesis and suppresses autophagy. Amino acid-induced activation of mammalian TORC1 is initiated by its recruitment to the RagA/B-RagC/D GTPase heterodimer, which is anchored to lysosomal membranes through the Ragulator complex. We have identified in the model organism Schizosaccharomyces pombe a Ragulator-like complex that tethers the Gtr1-Gtr2 Rag heterodimer to the membranes of vacuoles, the lysosome equivalent in yeasts. Unexpectedly, the Ragulator-Rag complex is not required for the vacuolar targeting of TORC1, but the complex plays a crucial role in attenuating TORC1 activity independently of the Tsc1-Tsc2 complex, a known negative regulator of TORC1 signaling. The GATOR1 complex, which functions as Gtr1 GAP, is essential for the TORC1 attenuation by the Ragulator-Rag complex, suggesting that Gtr1GDP-Gtr2 on vacuolar membranes moderate TORC1 signaling for optimal cellular response to nutrients.

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Author details

  1. Kim Hou Chia

    Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7958-6635
  2. Tomoyuki Fukuda

    Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
    For correspondence
    tfukuda@med.niigata-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
  3. Fajar Sofyantoro

    Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Takato Matsuda

    Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Takamitsu Amai

    Graduate School of Biological Science, Nara Institute of Science and Technology, Ikoma, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Kazuhiro Shiozaki

    Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan
    For correspondence
    kaz@bs.naist.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0395-5457

Funding

Japan Society for the Promotion of Science (26840069)

  • Tomoyuki Fukuda

Suzuken Memorial Foundation

  • Tomoyuki Fukuda

Japan Society for the Promotion of Science (17K07330)

  • Tomoyuki Fukuda

Japan Society for the Promotion of Science (26291024)

  • Kazuhiro Shiozaki

Ministry of Education, Culture, Sports, Science, and Technology (Graduate Student Scholarship)

  • Kim Hou Chia

Panasonic Corporation (Graduate Student Scholarship)

  • Fajar Sofyantoro

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

Publication history

  1. Received: July 29, 2017
  2. Accepted: December 2, 2017
  3. Accepted Manuscript published: December 4, 2017 (version 1)
  4. Version of Record published: January 3, 2018 (version 2)

Copyright

© 2017, Chia 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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