Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar;32(3):1154-1169.
doi: 10.1096/fj.201700763R. Epub 2018 Jan 3.

G protein-dependent signaling triggers a β-arrestin-scaffolded p70S6K/ rpS6 module that controls 5'TOP mRNA translation

Aurélie Tréfier  1   2   3   4 , Astrid Musnier  1   2   3   4 , Flavie Landomiel  1   2   3   4 , Thomas Bourquard  1   2   3   4 , Thomas Boulo  1   2   3   4 , Mohammed Akli Ayoub  1   2   3   4   5 , Kelly León  1   2   3   4 , Gilles Bruneau  1   2   3   4 , Manon Chevalier  1   2   3   4 , Guillaume Durand  1   2   3   4 , Marie-Claire Blache  6   2   3   4 , Asuka Inoue  7 , Joël Fontaine  1   2   3   4 , Christophe Gauthier  1   2   3   4 , Sophie Tesseraud  8 , Eric Reiter  1   2   3   4 , Anne Poupon  1   2   3   4 , Pascale Crépieux  1   2   3   4
Affiliations

G protein-dependent signaling triggers a β-arrestin-scaffolded p70S6K/ rpS6 module that controls 5'TOP mRNA translation

Aurélie Tréfier et al. FASEB J. 2018 Mar.

Abstract

Many interaction partners of β-arrestins intervene in the control of mRNA translation. However, how β-arrestins regulate this cellular process has been poorly explored. In this study, we show that β-arrestins constitutively assemble a p70S6K/ribosomal protein S6 (rpS6) complex in HEK293 cells and in primary Sertoli cells of the testis. We demonstrate that this interaction is direct, and experimentally validate the interaction interface between β-arrestin 1 and p70S6K predicted by our docking algorithm. Like most GPCRs, the biological function of follicle-stimulating hormone receptor (FSHR) is transduced by G proteins and β-arrestins. Upon follicle-stimulating hormone (FSH) stimulation, activation of G protein-dependent signaling enhances p70S6K activity within the β-arrestin/p70S6K/rpS6 preassembled complex, which is not recruited to the FSHR. In agreement, FSH-induced rpS6 phosphorylation within the β-arrestin scaffold was decreased in cells depleted of Gαs. Integration of the cooperative action of β-arrestin and G proteins led to the translation of 5' oligopyrimidine track mRNA with high efficacy within minutes of FSH input. Hence, this work highlights new relationships between G proteins and β-arrestins when acting cooperatively on a common signaling pathway, contrasting with their previously shown parallel action on the ERK MAP kinase pathway. In addition, this study provides insights into how GPCR can exert trophic effects in the cell.-Tréfier, A., Musnier, A., Landomiel, F., Bourquard, T., Boulo, T., Ayoub, M. A., León, K., Bruneau, G., Chevalier, M., Durand, G., Blache, M.-C., Inoue, A., Fontaine, J., Gauthier, C., Tesseraud, S., Reiter, E., Poupon, A., Crépieux, P. G protein-dependent signaling triggers a β-arrestin-scaffolded p70S6K/ rpS6 module that controls 5'TOP mRNA translation.

Keywords: FSHR; GPCR; gene regulation.

PubMed Disclaimer

Publication types

LinkOut - more resources