Plasma membrane translocation of REDD1 governed by GPCRs contributes to mTORC1 activation

Journal of Cell Science
Grégory MichelSandra Lecat

Abstract

The mTORC1 kinase promotes cell growth in response to growth factors by activation of receptor tyrosine kinase. It is regulated by the cellular energy level and the availability of nutrients. mTORC1 activity is also inhibited by cellular stresses through overexpression of REDD1 (regulated in development and DNA damage responses). We report the identification of REDD1 in a fluorescent live-imaging screen aimed at discovering new proteins implicated in G-protein-coupled receptor signaling, based on translocation criteria. Using a sensitive and quantitative plasma membrane localization assay based on bioluminescent resonance energy transfer, we further show that a panel of endogenously expressed GPCRs, through a Ca(2+)/calmodulin pathway, triggers plasma membrane translocation of REDD1 but not of its homolog REDD2. REDD1 and REDD2 share a conserved mTORC1-inhibitory motif characterized at the functional and structural level and differ most in their N-termini. We show that the N-terminus of REDD1 and its mTORC1-inhibitory motif participate in the GPCR-evoked dynamic interaction of REDD1 with the plasma membrane. We further identify REDD1 as a novel effector in GPCR signaling. We show that fast activation of mTORC1 by GPCRs correlat...Continue Reading

References

Jul 1, 1994·Trends in Pharmacological Sciences·D R Edwards
May 31, 2001·The Journal of Cell Biology·T M SavinoD Hernandez-Verdun
Dec 14, 2001·The Journal of Biological Chemistry·Hervé GicquiauxJean-Luc Galzi
Apr 23, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gerry ShawFrank L Graham
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 6, 2004·The Journal of Biological Chemistry·Laurence CézanneAndré Lopez
Jan 6, 2005·The Journal of Biological Chemistry·Michael N CorradettiKun-Liang Guan
Jul 1, 2005·Molecular and Cellular Biology·Avi SoferLeif W Ellisen
Nov 11, 2005·The Journal of Biological Chemistry·Sudha K ShenoyRobert J Lefkowitz
Jul 22, 2006·Protein Engineering, Design & Selection : PEDS·Andreas Markus LoeningSanjiv Sam Gambhir
Nov 18, 2006·Methods in Enzymology·Christine C HudsonCarson R Loomis
Jul 31, 2007·Trends in Pharmacological Sciences·Ségolène GalandrinMichel Bouvier
Sep 6, 2007·Journal of Cellular Physiology·Enrique Rozengurt
Dec 19, 2007·The Journal of Biological Chemistry·Matthew T DrakeRobert J Lefkowitz
Dec 25, 2007·Methods in Cell Biology·J R De MeyJ-B Sibarita
Jan 17, 2008·Genes & Development·Maurice Phillip DeYoungLeif W Ellisen
Jun 17, 2008·The Journal of Biological Chemistry·Muriel Hachet-HaasJean-Luc Galzi
Dec 23, 2008·Trends in Pharmacological Sciences·Avais M DaulatRalf Jockers
Jan 9, 2009·American Journal of Physiology. Cell Physiology·Mitsunori Miyazaki, Karyn A Esser
Aug 8, 2009·Journal of Molecular and Cellular Cardiology·Jean-Pierre BenitahAna María Gómez
Oct 2, 2009·Journal of Cellular Biochemistry·Robert A FrostCharles H Lang
Nov 6, 2009·Cellular Signalling·Astrid MusnierPascale Crépieux
Dec 10, 2009·The Journal of Biological Chemistry·Claire RegazzettiSophie Giorgetti-Peraldi
Feb 20, 2010·Biochemistry·Silvia Vega-Rubin-de-CelisXuewu Zhang

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Citations

Apr 23, 2014·Trends in Endocrinology and Metabolism : TEM·Eric M WausonMelanie H Cobb
Oct 18, 2014·Frontiers in Cellular Neuroscience·Mercè CanalCristina Malagelada
May 18, 2016·American Journal of Physiology. Endocrinology and Metabolism·Bradley S GordonScot R Kimball
Sep 6, 2017·Scientific Reports·Laurie-Anne RoeckelClaire Gaveriaux-Ruff
Aug 23, 2019·Cellular and Molecular Life Sciences : CMLS·Petronila PenelaFederico Mayor
Sep 14, 2017·American Journal of Physiology. Endocrinology and Metabolism·Bradley S GordonPaul M Coen
Aug 29, 2020·Genes·Chase H Melick, Jenna L Jewell
Sep 29, 2018·International Journal of Molecular Sciences·Hanne LeysenStuart Maudsley
Sep 3, 2020·American Journal of Physiology. Cell Physiology·Florian A BrittoFrancois B Favier

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