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

Open Access
Publisher Website
Google Scholar
Abstract
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.