Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
- Newcastle University, United Kingdom
- Massachusetts Institute of Technology, United States
- The Beatson Institute for Cancer Research, United Kingdom
- Cardiff University, United Kingdom
- University of Birmingham, United Kingdom
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is the key signalling hub that regulates cellular protein homeostasis, growth and proliferation. Herein, we demonstrate that amino acid arginine acts independent of its metabolism to allow maximal activation of mTORC1 by growth factors, via a mechanism that does not involve regulation of mTORC1 localization to lysosomes. Instead, arginine specifically suppresses lysosomal localization of the TSC complex and interaction with its target small GTPase protein, Rheb. By interfering with TSC-Rheb complex, arginine relieves allosteric inhibition of Rheb by TSC. Arginine is the main amino acid sensed by the mTORC1 pathway in several cell types including human embryonic stem cells (hESCs). Together, our data provide evidence that different growth promoting cues cooperate to a greater extent than previously recognized to achieve tight spatial and temporal regulation of mTORC1 signalling.
Article and author information
Author details
Reviewing Editor
- Noboru Mizushima, The University of Tokyo, Japan
Version history
- Received: August 21, 2015
- Accepted: December 30, 2015
- Accepted Manuscript published: January 7, 2016 (version 1)
- Version of Record published: February 10, 2016 (version 2)
- Version of Record updated: December 16, 2020 (version 3)
Copyright
© 2016, Carroll et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity
eLife 5:e11058.
https://doi.org/10.7554/eLife.11058
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