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    Home > Biochemistry News > Biotechnology News > Peking University Nature's latest paper: SAR1B senses intracellular leucine concentration and regulates mTORC1 activity

    Peking University Nature's latest paper: SAR1B senses intracellular leucine concentration and regulates mTORC1 activity

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    How cells perceive the state of nutrients so as to coordinate their growth is a basic issue in life sciences
    .
    Nutrients include amino acids, glucose and fatty acids

    .
    Among them, cells sense the concentration of amino acids through the mTORC1 complex, and regulate protein synthesis and cell growth accordingly

    .
    The concentration of various amino acids will be sensed by their corresponding receptor proteins (namely amino acid receptors)

    .

    On July 21, 2021, Professor Liu Ying's research group from the Institute of Molecular Medicine, Peking University Future Technology College, Peking University-Tsinghua Life Sciences Joint Center, and Beijing Future Gene Diagnosis Advanced Innovation Center published a titled "SAR1B senses leucine levels" on Nature Online to regulate mTORC1 signalling" research paper, reported the regulation mechanism of leucine receptor protein SAR1B on mTORC1 and its important physiological and pathological significance
    .

    Researchers discovered the receptor protein SAR1B of leucine through mass spectrometry experiments
    .
    The classic function of SAR1B is to participate in vesicle formation as a small G protease

    .
    The researchers found that SAR1B's perception of leucine does not depend on its classic small G protease activity

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    After SAR1B senses the leucine signal, it transmits the signal to mTORC1 through the GATOR2 complex (Figure 1)

    .
    In addition, the researchers used the invertebrate model organism nematode to prove that SAR1B perceives leucine as an evolutionarily highly conserved mechanism

    .
    The researchers used bioinformatics analysis and established a nude mouse lung orthotopic tumor model to prove that SAR1B acts as a tumor suppressor in the occurrence of lung cancer by inhibiting the activity of mTORC1 (Figure 2)

    .

    Figure 1.
    Molecular mechanism: (left) when leucine is lacking, SAR1B binds to and inhibits GATOR2, and mTORC1 is inactivated; (right) when leucine is sufficient, SAR1B binds to leucine and undergoes allosteric, dissociates GATOR2, and mTORC1 is deactivated activation

    Figure 2.
    Pathological significance: (left) a schematic diagram of the establishment of orthotopic tumors in the lungs of mice; (right) removal of SAR1B and its homologous protein SAR1A promotes tumor growth in the lungs of mice, and treatment with rapamycin, tumor growth is inhibited

    Dr.
    Chen Jie and Liu Ying from Peking University are the co-corresponding authors of this study

    .
    Chen Jie and Ou Yuhui, a doctoral student at the Institute of Molecular Medicine, School of Future Technology, Peking University, are the co-first authors

    .
    The research was funded by the National Natural Science Foundation of China, the National Key Research and Development Program of the Ministry of Science and Technology, the HHMI International Research Scholars Project, the Beijing Future Genetic Diagnosis Advanced Innovation Center, the Peking University-Tsinghua Life Science Joint Center, and the Science Exploration Award

    .


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