Glutamine and asparagine activate mTORC1 independently of Rag GTPases
Glutamine and asparagine activate mTORC1 independently of Rag GTPases
复制标题
DOI：
10.1074/jbc.ac119.011578
复制
发表时间：
2020-03-06
影响因子：
4.8
通讯作者：
Jewell, Jenna L.
中科院分区：
文献类型：
--
作者：
Meng, Delong;Yang, Qianmei;Jewell, Jenna L.
细胞对营养物质的感知至关重要，当这种感知机制受到干扰时，人类就会发生疾病。mTOR复合物1（mTORC 1）感测氨基酸以控制细胞生长、代谢和自噬。亮氨酸、精氨酸和甲硫氨酸通过充分表征的Rag GT3信号传导途径向mTORC 1发出信号。与此相反，谷氨酰胺激活mTORC 1通过一个拉格GTALGORITHM？需要ADP-核糖基化因子1（Arf 1）的独立机制。在这里，使用几种生物化学和遗传学方法，我们表明，八个氨基酸过滤通过拉格谷氨酰胺途径。与谷氨酰胺一样，在不存在Rag GTP酶的情况下，天冬酰胺通过Arf 1向mTORC 1发出信号。Rag依赖性和Rag非依赖性途径都需要溶酶体和溶酶体功能来激活mTORC 1。我们的研究结果表明，mTORC 1是差异调节的氨基酸通过两个不同的途径。
Nutrient sensing by cells is crucial, and when this sensing mechanism is disturbed, human disease can occur. mTOR complex 1 (mTORC1) senses amino acids to control cell growth, metabolism, and autophagy. Leucine, arginine, and methionine signal to mTORC1 through the well-characterized Rag GTPase signaling pathway. In contrast, glutamine activates mTORC1 through a Rag GTPase?independent mechanism that requires ADP-ribosylation factor 1 (Arf1). Here, using several biochemical and genetic approaches, we show that eight amino acids filter through the Rag GTPase pathway. Like glutamine, asparagine signals to mTORC1 through Arf1 in the absence of the Rag GTPases. Both the Rag-dependent and Rag-independent pathways required the lysosome and lysosomal function for mTORC1 activation. Our results show that mTORC1 is differentially regulated by amino acids through two distinct pathways.