Glutamine and asparagine activate mTORC1 independently of Rag GTPases

Delong Meng, Qianmei Yang, Huanyu Wang, Chase H. Melick, Rishika Navlani, Anderson R. Frank, Jenna L. Jewell

Research output: Contribution to journalReview articlepeer-review

85 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2890-2899
Number of pages10
JournalJournal of Biological Chemistry
Issue number10
StatePublished - Mar 6 2020

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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