Requirement for lysosomal localization of mTOR for its activation differs between leucine and other amino acids

Julien Averous, Sarah Lambert-Langlais, Valérie Carraro, Ophélie Gourbeyre, Laurent Parry, Wafa B'Chir, Yuki Muranishi, Céline Jousse, Alain Bruhat, Anne Catherine Maurin, Christopher G. Proud, Pierre Fafournoux

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth and metabolism. It controls many cell functions by integrating nutrient availability and growth factor signals. Amino acids, and in particular leucine, are among the main positive regulators of mTORC1 signaling. The current model for the regulation of mTORC1 by amino acids involves the movement of mTOR to the lysosome mediated by the Rag-GTPases. Here, we have examined the control of mTORC1 signaling and mTOR localization by amino acids and leucine in serum-fed cells, because both serum growth factors (or, e.g., insulin) and amino acids are required for full activation of mTORC1 signaling. We demonstrate that mTORC1 activity does not closely correlate with the lysosomal localization of mTOR. In particular, leucine controls mTORC1 activity without any detectable modification of the lysosomal localization of mTOR, indicating that the signal(s) exerted by leucine is likely distinct from those exerted by other amino acids. In addition, knock-down of the Rag-GTPases attenuated the inhibitory effect of amino acid- or leucine-starvation on the phosphorylation of mTORC1 targets. Furthermore, data from cells where Rag expression has been knocked down revealed that leucine can promote mTORC1 signaling independently of the lysosomal localization of mTOR. Our data complement existing models for the regulation of mTORC1 by amino acids and provide new insights into this important topic.

Original languageEnglish
Pages (from-to)1918-1927
Number of pages10
JournalCellular Signalling
Volume26
Issue number9
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • Amino acids
  • Leucine
  • Lysosome
  • MTORC1
  • Rags

ASJC Scopus subject areas

  • Cell Biology

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