Differential regulation of mTORC1 by leucine and glutamine

作者：Jewell, Jenna L.; Kim, Young Chul; Russell, Ryan C.; Yu, Fa-Xing; Park, Hyun Woo; Plouffe, Steven W.; Tagliabracci, Vincent S.; Guan, Kun-Liang^*

来源：Science, 2015, 347(6218): 194-198.

DOI：10.1126/science.1259472

• AMINO-ACID SUFFICIENCY
• P70 S6 KINASE
• RAG GTPASES
• COMPLEX
• PROTEINS
• ARF
• ACTIVATION
• RAGULATOR
• MECHANISM
• REVEALS

The mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) integrates environmental and intracellular signals to regulate cell growth. Amino acids stimulatem TORC1 activation at the lysosome in a manner thought to be dependent on the Rag small guanosine triphosphatases (GTPases), the Ragulator complex, and the vacuolar H+-adenosine triphosphatase (v-ATPase). We report that leucine and glutamine stimulate mTORC1 by Rag GTPase-dependent and -independent mechanisms, respectively. Glutamine promoted mTORC1 translocation to the lysosome in RagA and RagB knockout cells and required the v-ATPase but not the Ragulator. Furthermore, we identified the adenosine diphosphate ribosylation factor-1 GTPase to be required for mTORC1 activation and lysosomal localization by glutamine. Our results uncover a signaling cascade to mTORC1 activation independent of the Rag GTPases and suggest that mTORC1 is differentially regulated by specific amino acids.

• 出版日期2015-1-9
• 单位复旦大学