Regulation of TORC1 by Rag GTPases in nutrient response

Eunjung Kim, Pankuri Goraksha-Hicks, Li Li, Thomas P. Neufeld, Kun Liang Guan

Research output: Contribution to journalArticlepeer-review

833 Scopus citations

Abstract

TORC1 (target of rapamycin complex 1) has a crucial role in the regulation of cell growth and size. A wide range of signals, including amino acids, is known to activate TORC1. Here, we report the identification of Rag GTPases as activators of TORC1 in response to amino acid signals. Knockdown of Rag gene expression suppressed the stimulatory effect of amino acids on TORC1 in Drosophila melanogaster S2 cells. Expression of constitutively active (GTP-bound) Rag in mammalian cells activated TORC1 in the absence of amino acids, whereas expression of dominant-negative Rag blocked the stimulatory effects of amino acids on TORC1. Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals.

Original languageEnglish (US)
Pages (from-to)935-945
Number of pages11
JournalNature Cell Biology
Volume10
Issue number8
DOIs
StatePublished - 2008

Bibliographical note

Funding Information:
The authors wish to thank Ken Inoki for discussions and Mary Stewart for the dS6K antibody. This work is supported by NIH grants to K.L.G. (GM62694 and CA108941) and T.P.N. (GM62509).

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