SAR1B senses leucine levels to regulate mTORC1 signalling

Jie Chen (), Yuhui Ou, Rong Luo, Jie Wang, Dong Wang, Jialiang Guan, Yi Li, Peixue Xia, Peng R. Chen and Ying Liu ()
Additional contact information
Jie Chen: Peking University
Yuhui Ou: Peking University
Rong Luo: Peking University
Jie Wang: Peking University
Dong Wang: Peking University
Jialiang Guan: Peking University
Yi Li: Peking University
Peixue Xia: Peking University
Peng R. Chen: Peking University
Ying Liu: Peking University

Nature, 2021, vol. 596, issue 7871, 281-284

Abstract: Abstract The mTOR complex 1 (mTORC1) controls cell growth in response to amino acid levels1. Here we report SAR1B as a leucine sensor that regulates mTORC1 signalling in response to intracellular levels of leucine. Under conditions of leucine deficiency, SAR1B inhibits mTORC1 by physically targeting its activator GATOR2. In conditions of leucine sufficiency, SAR1B binds to leucine, undergoes a conformational change and dissociates from GATOR2, which results in mTORC1 activation. SAR1B–GATOR2–mTORC1 signalling is conserved in nematodes and has a role in the regulation of lifespan. Bioinformatic analysis reveals that SAR1B deficiency correlates with the development of lung cancer. The silencing of SAR1B and its paralogue SAR1A promotes mTORC1-dependent growth of lung tumours in mice. Our results reveal that SAR1B is a conserved leucine sensor that has a potential role in the development of lung cancer.

Date: 2021
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DOI: 10.1038/s41586-021-03768-w

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