Melanocortin Receptor Accessory Protein 2-Induced Adrenocorticotropic Hormone Response of Human Melanocortin 4 Receptor.
Journal
Journal of the Endocrine Society
ISSN: 2472-1972
Titre abrégé: J Endocr Soc
Pays: United States
ID NLM: 101697997
Informations de publication
Date de publication:
01 Feb 2019
01 Feb 2019
Historique:
received:
07
11
2018
accepted:
03
12
2018
entrez:
18
1
2019
pubmed:
18
1
2019
medline:
18
1
2019
Statut:
epublish
Résumé
Melanocortin 4 receptor (MC4R), a canonical melanocyte-stimulating hormone receptor, is the main responsible for monogenic obesity in humans. Previous studies in fish and avian species showed that MC4R becomes an ACTH receptor after interaction with the melanocortin receptor accessory protein 2 (MRAP2). We show that human MC4R behaves in a similar way through its interaction with MRAP2. This evolutionary conservation of MRAP2-induced ligand selectivity supports a physiological role for the interaction with MC4R. Both proteins are coexpressed in the same hypothalamic neurons, providing an anatomical substrate and molecular mechanism for the central therapeutic actions of ACTH in the treatment of infantile spasms. These neurons may link the effects of stress on the energy balance independently of glucocorticoid secretion. The complex MC4R-MRAP2 throws light on the action of ACTH and, by extension, on the relay of stress-related information to additional biological systems.
Identifiants
pubmed: 30652132
doi: 10.1210/js.2018-00370
pii: js_201800370
pmc: PMC6330173
doi:
Types de publication
Journal Article
Langues
eng
Pagination
314-323Références
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