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MRAP2 regulates ghrelin receptor signaling and hunger sensing

Author

Listed:
  • Dollada Srisai

    (University of Iowa, Carver College of Medicine
    F.O.E.D.R.C
    Pappajohn Biomedical Institute)

  • Terry C. Yin

    (University of Iowa, Carver College of Medicine
    F.O.E.D.R.C
    Pappajohn Biomedical Institute)

  • Abigail A. Lee

    (University of Iowa, Carver College of Medicine
    F.O.E.D.R.C
    Pappajohn Biomedical Institute)

  • Alix A. J. Rouault

    (University of Iowa, Carver College of Medicine
    F.O.E.D.R.C
    Pappajohn Biomedical Institute)

  • Nicole A. Pearson

    (F.O.E.D.R.C
    University of Iowa, Carver College of Medicine)

  • Justin L. Grobe

    (F.O.E.D.R.C
    University of Iowa, Carver College of Medicine)

  • Julien A. Sebag

    (University of Iowa, Carver College of Medicine
    F.O.E.D.R.C
    Pappajohn Biomedical Institute)

Abstract

Ghrelin is the only known circulating orexigenic hormone. It is primarily secreted by the stomach and acts at its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), in the hypothalamus to signal hunger and promote food intake. The melanocortin receptor accessory protein 2 (MRAP2) was previously shown to regulate energy homeostasis through the modulation of the activity of the melanocortin-4 receptor and prokineticin receptors. In this study we identify MRAP2 as a partner of ghrelin-GHSR1a signaling. We show that MRAP2 interacts with GHSR1a and potentiates ghrelin-stimulated signaling both in vitro and in vivo. We demonstrate that in the absence of MRAP2, fasting fails to activate agouti-related protein neurons. In addition, we show that the orexigenic effect of ghrelin is lost in mice lacking MRAP2. Our results suggest that MRAP2 is an important modulator of the energy homeostasis machinery that operates through the regulation of multiple GPCRs throughout the hypothalamus.

Suggested Citation

  • Dollada Srisai & Terry C. Yin & Abigail A. Lee & Alix A. J. Rouault & Nicole A. Pearson & Justin L. Grobe & Julien A. Sebag, 2017. "MRAP2 regulates ghrelin receptor signaling and hunger sensing," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00747-6
    DOI: 10.1038/s41467-017-00747-6
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    Cited by:

    1. Heng Liu & Dapeng Sun & Alexander Myasnikov & Marjorie Damian & Jean-Louis Baneres & Ji Sun & Cheng Zhang, 2021. "Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren," Nature Communications, Nature, vol. 12(1), pages 1-8, December.

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