Developmental Control of the Melanocortin-4 Receptor by MRAP2 Proteins in Zebrafish

Julien A Sebag; Chao Zhang; Patricia M Hinkle; Amanda M Bradshaw; Roger D Cone

doi:10.1126/science.1232995

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Developmental Control of the Melanocortin-4 Receptor by MRAP2 Proteins in Zebrafish

Journal article

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Developmental Control of the Melanocortin-4 Receptor by MRAP2 Proteins in Zebrafish

Julien A Sebag, Chao Zhang, Patricia M Hinkle, Amanda M Bradshaw and Roger D Cone

Science (American Association for the Advancement of Science), Vol.341(6143), pp.278-281

07/19/2013

DOI: 10.1126/science.1232995

PMCID: PMC4255277

PMID: 23869017

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Abstract

The melanocortin-4 receptor (MC4R) is essential for control of energy homeostasis in vertebrates. MC4R interacts with melanocortin receptor accessory protein 2 (MRAP2) in vitro, but its functions in vivo are unknown. We found that MRAP2a, a larval form, stimulates growth of zebrafish by specifically blocking the action of MC4R. In cell culture, this protein binds MC4R and reduces the ability of the receptor to bind its ligand, α–melanocyte-stimulating hormone (α-MSH). A paralog, MRAP2b, expressed later in development, also binds MC4R but increases ligand sensitivity. Thus, MRAP2 proteins allow for developmental control of MC4R activity, with MRAP2a blocking its function and stimulating growth during larval development, whereas MRAP2b enhances responsiveness to α-MSH once the zebrafish begins feeding, thus increasing the capacity for regulated feeding and growth.

Details

Title: Subtitle: Developmental Control of the Melanocortin-4 Receptor by MRAP2 Proteins in Zebrafish
Creators: Julien A Sebag - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Chao Zhang - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Patricia M Hinkle - Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, NY 14642, USA
Amanda M Bradshaw - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Roger D Cone - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Resource Type: Journal article
Publication Details: Science (American Association for the Advancement of Science), Vol.341(6143), pp.278-281
DOI: 10.1126/science.1232995
PMID: 23869017
PMCID: PMC4255277
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Language: English
Date published: 07/19/2013
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984025404002771

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