期刊
MOLECULAR CELL
卷 81, 期 2, 页码 398-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2020.11.036
关键词
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资金
- Canadian Institutes of Health Research (CIHR) Foundation [FDN-148423, FDN-143301]
- National Research Foundation of Korea (NRF) - Ministry of Education [2019R1A6A3A03034060]
- Canderel Postdoctoral Fellowship
- Fonds de recherche du Quebec -Sante (FRQS) Postdoctoral Fellowship
- Frederick Banting and Charles Best Canada Graduate Scholarship
- Parkinson Canada Basic Research Fellowship
- Patrick Johnston Research Fellowship at Queen's University Belfast
- UK Medical Research Council (MRC) [R1135CNR]
- National Research Foundation of Korea [2019R1A6A3A03034060] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
This study reveals a new pathway for activating mTORC1 in response to variations in threonine levels through mitochondrial synthetase TARS2. The interaction between TARS2 and Rags increases GTP loading of RagA, influencing the activity of mTORC1.
Mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and proliferation by sensing fluctuations in environmental cues such as nutrients, growth factors, and energy levels. The Rag GTPases (Rags) serve as a critical module that signals amino acid (AA) availability to modulate mTORC1 localization and activity. Recent studies have demonstrated how AAs regulate mTORC1 activity through Rags. Here, we uncover an unconventional pathway that activates mTORC1 in response to variations in threonine (Thr) levels via mitochondrial threonyl-tRNA synthetase TARS2. TARS2 interacts with inactive Rags, particularly GTP-RagC, leading to increased GTP loading of RagA. mTORC1 activity in cells lacking TARS2 is resistant to Thr repletion, showing that TARS2 is necessary for Thr-dependent mTORC1 activation. The requirement of TARS2, but not cytoplasmic threonyl-tRNA synthetase TARS, for this effect demonstrates an additional layer of complexity in the regulation of mTORC1 activity.
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