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

Aurélie Tréfier, Astrid Musnier, Flavie Landomiel, Thomas Bourquard, Thomas Boulo, Mohammed Akli Ayoub, Kelly León, Gilles Bruneau, Manon Chevalier, Guillaume Durand, Marie Claire Blache, Asuka Inoue, Joël Fontaine, Christophe Gauthier, Sophie Tesseraud, Eric Reiter, Anne Poupon, Pascale Crépieux

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


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 inHEK293 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 folliclestimulating 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 59 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 ERKMAP kinase pathway. In addition, this study provides insights into howGPCR can exert trophic effects in the cell.

Original languageEnglish
Pages (from-to)1154-1169
Number of pages16
JournalFASEB Journal
Issue number3
Publication statusPublished - Mar 2018


  • FSHR
  • GPCR
  • Gene regulation

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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