G-protein-coupled receptors (GPCRs) are a structurally conserved family of plasma membrane receptors that trigger intracellular signalling pathways through the activation of heterotrimeric G-proteins. To uncover new components of the GPCR pathway, Sandra Lecat and colleagues perform a translocation assay in living cells by screening a library of fluorescently modified proteins of unknown function for changes in their intracellular localisation upon GPCR activation (p. 773). REDD1 (also known as DDIT4) yielded a hit in this screen and the authors then confirm its translocation to the plasma membrane after activation of different GPCRs. REDD1 contains a mammalian target of rapamycin kinase (mTORC1) inhibitory motif that the authors now found to be necessary for its association with the plasma membrane; a discovery that prompted them to investigate its effect on the mTOR pathway. Indeed, mTORC1 activation in response to GPCRs correlates with fast translocation of REDD1 to the plasma membrane, presumably sequestering the mTORC1-inhibitory motif and thus releasing mTORC1 inhibition. Consistently, REDD1 overexpression leads to reduced mTORC1 activation by GPCRs, whereas depletion of REDD1 increases mTORC1 activity. Taken together, this study suggests that the mTOR pathway acts downstream of GPCR signaling through the newly identified link REDD1, thus pointing to additional crosstalk between the receptor tyrosine kinase signalling pathways upstream of mTOR and GPCR signalling that might be relevant in the context of different physiological conditions.
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IN THIS ISSUE| 15 February 2014
REDD1 – linking GPCRs and mTOR
Online Issn: 1477-9137
Print Issn: 0021-9533
© 2014. Published by The Company of Biologists Ltd
J Cell Sci (2014) 127 (4): e0405.
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REDD1 – linking GPCRs and mTOR. J Cell Sci 15 February 2014; 127 (4): e0405. doi:
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