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SAR1B senses leucine levels to regulate mTORC1 signalling
Jie Chen1,2, Yuhui Ou3, Rong Luo4
1State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, China. chen.jie@pku.edu.cn.
Nature
|July 22, 2021
Summary
Scientists discovered SAR1B as a leucine sensor regulating cell growth by controlling mTORC1 signaling. This discovery reveals SAR1B
Area of Science:
- Cellular Biology
- Molecular Biology
- Biochemistry
Background:
- The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth.
- mTORC1 activity is known to be sensitive to intracellular amino acid levels.
Purpose of the Study:
- To identify the molecular mechanisms linking intracellular leucine levels to mTORC1 signaling.
- To investigate the role of SAR1B in sensing leucine and regulating mTORC1.
Main Methods:
- Biochemical assays to study protein-protein interactions.
- Cellular assays to monitor mTORC1 signaling.
- Bioinformatic analysis of gene expression data.
- In vivo studies using mouse models of lung cancer.
Main Results:
- SAR1B acts as a direct sensor for intracellular leucine.
- Leucine binding induces a conformational change in SAR1B, leading to its dissociation from GATOR2.
- Dissociation of SAR1B from GATOR2 activates mTORC1 signaling.
- SAR1B-GATOR2-mTORC1 pathway is conserved in nematodes and affects lifespan.
- SAR1B deficiency correlates with lung cancer development.
- Silencing of SAR1B and SAR1A promotes tumor growth in mice.
Conclusions:
- SAR1B is a crucial leucine sensor that modulates mTORC1 signaling.
- The SAR1B-GATOR2-mTORC1 pathway plays a significant role in cell growth regulation.
- SAR1B has potential implications in the development and progression of lung cancer.
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