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  • The EMBO Journal (2007) 26, 1522 - 1531
  • doi:10.1038/sj.emboj.7601598

Published online: 22 February 2007

The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation

Nien-Pei Tsai1, Jing Bi1 and Li-Na Wei1

  1. Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN, USA

Correspondence to:

Li-Na Wei, Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA. Tel.: +1 612 6259402; Fax: +1 612 6258408, E-mail: weixx009@umn.edu

Received 14 October 2006; Accepted 8 January 2007

We previously reported a novel biological activity of Netrin-1 in translational stimulation of kappa opioid receptor (KOR). We now identify Grb7 as a new RNA-binding protein that serves as the molecular adaptor for transmitting Netrin-1 signals, through focal adhesion kinase (FAK), to the translation machinery. Grb7 binds specifically to the first stem loop of kor mRNA 5'-UTR through a new RNA-binding domain located in its amino terminus. Upon binding to its capped, target mRNA, Grb7 blocks the recruitment of eIF4E, rendering mRNA untranslatable. The RNA-binding and translation-repressive activity is reduced by FAK-mediated hyperphosphorylation on two tyrosine residues of its carboxyl terminus. This study reports an adaptor protein Grb7 that transmits the stimulating signals of Netrin-1 to the translational machinery to rapidly regulate mRNA translation.

  • Keywords:

    • Grb7,
    • Netrin-1,
    • RNA-binding protein,
    • translation