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SAR1B senses leucine levels to regulate mTORC1 signalling

Author

Listed:
  • Jie Chen

    (Peking University
    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
    Peking University)

  • Peixue Xia

    (Peking University)

  • Peng R. Chen

    (Peking University
    Peking University)

  • Ying Liu

    (Peking University
    Peking University
    Beijing Advanced Innovation Center for Genomics)

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.

Suggested Citation

  • Jie Chen & Yuhui Ou & Rong Luo & Jie Wang & Dong Wang & Jialiang Guan & Yi Li & Peixue Xia & Peng R. Chen & Ying Liu, 2021. "SAR1B senses leucine levels to regulate mTORC1 signalling," Nature, Nature, vol. 596(7871), pages 281-284, August.
    • Handle: RePEc:nat:nature:v:596:y:2021:i:7871:d:10.1038_s41586-021-03768-w
    DOI: 10.1038/s41586-021-03768-w
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    Cited by:

    1. Wennan Zhao & Xue Wang & Lifeng Han & Chunze Zhang & Chenxi Wang & Dexin Kong & Mingzhe Zhang & Tong Xu & Gen Li & Ge Hu & Jiahua Luo & Sook Wah Yee & Jia Yang & Andreas Stahl & Xin Chen & Youcai Zhan, 2024. "SLC13A3 is a major effector downstream of activated β-catenin in liver cancer pathogenesis," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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