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Melanocortin 4 Receptor Becomes an ACTH Receptor by Coexpression of Melanocortin Receptor Accessory Protein 2
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2013
- Publisher :
- Endocrine Society, 2013.
-
Abstract
- Melanocortin 2 receptor (MC2R) is the only canonical ACTH receptor. Its functional expression requires the presence of an accessory protein, known as melanocortin receptor 2 accessory protein 1 (MRAP1). The vertebrate genome exhibits a paralogue gene called MRAP2, which is duplicated in zebrafish (MRAP2a and MRAP2b), although its function remains unknown. In this paper, we demonstrate that MRAP2a enables MC4R, a canonical MSH receptor, to be activated by ACTH with a similar sensitivity to that exhibited by MC2R. Both proteins physically interact and are coexpressed in the neurons of the preoptic area, a key region in the control of the energy balance and hypophyseal secretion in fish. ACTH injections inhibit food intake in wild-type zebrafish but not in fish lacking functional MC4R. Both MRAP1 and MRAP2a are hormonally regulated, suggesting that these proteins are substrates for feed-back regulatory pathways of melanocortin signaling. Fasting has no effect on the central expression of MRAP2a but stimulates MRAP2b expression. This protein interacts and is colocalized with MC4R in the tuberal hypothalamic neurons but has no effect on the pharmacologic profile of MC4R. However, MRPA2b is able to decrease basal reporter activity in cell lines expressing MC4R. It is plausible that MRAP2b decreases the constitutive activity of the MC4R during fasting periods, driving the animal toward a positive energy balance. Our data indicate that MRAP2s control the activity of MC4R, opening up new pathways for the regulation of melanocortin signaling and, by extension, for the regulation of the energy balance and obesity. © 2013 by The Endocrine Society.
- Subjects :
- Male
medicine.medical_specialty
endocrine system
Hydrocortisone
Peroxisome Proliferator-Activated Receptors
Gene Expression
Biology
Endocrinology
Melanocortin receptor
Adrenocorticotropic Hormone
Internal medicine
Protein Interaction Mapping
medicine
Enzyme-linked receptor
Animals
Humans
ACTH receptor
5-HT5A receptor
Molecular Biology
Zebrafish
Original Research
Intracellular Signaling Peptides and Proteins
General Medicine
Zebrafish Proteins
Melanocortin 3 receptor
Melanocortin 4 receptor
Protein Transport
HEK293 Cells
Receptors, Corticotropin
Receptor, Melanocortin, Type 4
Triiodothyronine
Female
Signal transduction
Melanocortin
Bezafibrate
Carrier Proteins
Energy Intake
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Accession number :
- edsair.doi.dedup.....6df2e3880a71e0bb631379b721c515de