Publication Date:
2013-07-23
Description:
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, alpha-melanocyte-stimulating hormone (alpha-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 alpha-MSH once the zebrafish begins feeding, thus increasing the capacity for regulated feeding and growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255277/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255277/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sebag, Julien A -- Zhang, Chao -- Hinkle, Patricia M -- Bradshaw, Amanda M -- Cone, Roger D -- DK020593/DK/NIDDK NIH HHS/ -- DK070332/DK/NIDDK NIH HHS/ -- DK075721/DK/NIDDK NIH HHS/ -- DK19974/DK/NIDDK NIH HHS/ -- F23DK091055/DK/NIDDK NIH HHS/ -- R01 DK070332/DK/NIDDK NIH HHS/ -- R01 DK075721/DK/NIDDK NIH HHS/ -- T32 DK007563/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 19;341(6143):278-81. doi: 10.1126/science.1232995.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23869017" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Embryo, Nonmammalian/metabolism
;
Energy Metabolism
;
HEK293 Cells
;
Humans
;
Receptor Activity-Modifying Proteins/genetics/*metabolism
;
Receptor, Melanocortin, Type 4/*metabolism
;
Zebrafish/*embryology/metabolism
;
Zebrafish Proteins/genetics/*metabolism
;
alpha-MSH/metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
