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.

mTOR 复合物 1 (mTORC1) 控制细胞生长以响应氨基酸水平¹. 在这里，我们将 SAR1B 报告为亮氨酸传感器，它调节 mTORC1 信号以响应细胞内亮氨酸水平。在亮氨酸缺乏的情况下，SAR1B 通过物理靶向其激活剂 GATOR2 来抑制 mTORC1。在亮氨酸充足的条件下，SAR1B 与亮氨酸结合，发生构象变化并与 GATOR2 解离，从而导致 mTORC1 激活。SAR1B–GATOR2–mTORC1 信号在线虫中是保守的，并且在寿命调节中起作用。生物信息学分析表明，SAR1B 缺陷与肺癌的发展相关。SAR1B 及其旁系同源物 SAR1A 的沉默促进了小鼠肺肿瘤的 mTORC1 依赖性生长。我们的结果表明 SAR1B 是一种保守的亮氨酸传感器，在肺癌的发展中具有潜在作用。