Research ArticleGPCR SIGNALING

The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a

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Science Signaling  07 Jan 2020:
Vol. 13, Issue 613, eaax4569
DOI: 10.1126/scisignal.aax4569

Skewing signaling with an accessory protein

Ghrelin is a peptide that is secreted by the stomach during fasting to promote food intake. The accessory protein MRAP2 interacts with the ghrelin receptor GHSR1a and is important for the orexigenic effects of ghrelin. Rouault et al. found that MRAP2 promoted biased signaling downstream of ghrelin-mediated activation of GHSR1a by inhibiting β-arrestin recruitment to the receptor and potentiating Gαq/11-dependent signaling. Furthermore, MRAP2 suppressed ligand-independent activity of GHSR1a, which is naturally high. These results show that accessory proteins can bias GPCR signaling and, for GHSR1a, limit its constitutive activity.

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