Article abstract
Nature Cell Biology
Published online: 6 July 2008 | doi:10.1038/ncb1753
Regulation of TORC1 by Rag GTPases in nutrient response
Eunjung Kim1,3,4, Pankuri Goraksha-Hicks2,4, Li Li1, Thomas P. Neufeld2 & Kun-Liang Guan1
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.
- Department of Pharmacology and Moores Cancer Center, University of California San Diego, La Jolla, CA 92093-081, USA.
- Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.
- Current address: Department of Food Sciences and Nutrition, Catholic University of Daegu, Gyeongsan, Korea.
- These authors contributed equally to this study.
Correspondence to: Thomas P. Neufeld2 e-mail: neufe003@umn.edu
Correspondence to: Kun-Liang Guan1 e-mail: kuguan@ucsd.edu