Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases
- Nara Institute of Science and Technology, Japan
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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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.
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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Ragulator and GATOR1 complexes promote fission yeast growth by attenuating TOR complex 1 through Rag GTPases
eLife 6:e30880.
https://doi.org/10.7554/eLife.30880
