Melanocortin‐1 receptor structure and functional regulation
Identifieur interne : 000903 ( Main/Exploration ); précédent : 000902; suivant : 000904Melanocortin‐1 receptor structure and functional regulation
Auteurs : José C. García-Borr N [Espagne] ; Berta L. Sánchez-Laorden [Espagne] ; Celia Jiménez-Cervantes [Espagne]Source :
- Pigment Cell Research [ 0893-5785 ] ; 2005-12.
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Abstract
The melanogenic actions of the melanocortins are mediated by the melanocortin‐1 receptor (MC1R). MC1R is a member of the G‐protein‐coupled receptors (GPCR) superfamily expressed in cutaneous and hair follicle melanocytes. Activation of MC1R by adrenocorticotrophin or α‐melanocyte stimulating hormone is positively coupled to the cAMP signaling pathway and leads to a stimulation of melanogenesis and a switch from the synthesis of pheomelanins to the production of eumelanic pigments. The functional behavior of the MC1R agrees with emerging concepts in GPCR signaling including dimerization, coupling to more than one signaling pathway and a high agonist‐independent constitutive activity accounting for inverse agonism phenomena. In addition, MC1R displays unique properties such as an unusually high number of natural variants often associated with clearly visible phenotypes and the occurrence of endogenous peptide antagonists. Therefore MC1R is an ideal model to study GPCR function. Here we review our current knowledge of MC1R structure and function, with emphasis on information gathered from the analysis of natural variants. We also discuss recent data on the regulation of MC1R function by paracrine and endocrine factors and by external stimuli such as ultraviolet light.
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DOI: 10.1111/j.1600-0749.2005.00278.x
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MC1R is a member of the G‐protein‐coupled receptors (GPCR) superfamily expressed in cutaneous and hair follicle melanocytes. Activation of MC1R by adrenocorticotrophin or α‐melanocyte stimulating hormone is positively coupled to the cAMP signaling pathway and leads to a stimulation of melanogenesis and a switch from the synthesis of pheomelanins to the production of eumelanic pigments. The functional behavior of the MC1R agrees with emerging concepts in GPCR signaling including dimerization, coupling to more than one signaling pathway and a high agonist‐independent constitutive activity accounting for inverse agonism phenomena. In addition, MC1R displays unique properties such as an unusually high number of natural variants often associated with clearly visible phenotypes and the occurrence of endogenous peptide antagonists. Therefore MC1R is an ideal model to study GPCR function. Here we review our current knowledge of MC1R structure and function, with emphasis on information gathered from the analysis of natural variants. We also discuss recent data on the regulation of MC1R function by paracrine and endocrine factors and by external stimuli such as ultraviolet light.</div></front></TEI><affiliations><list><country><li>Espagne</li></country></list><tree><country name="Espagne"><noRegion><name sortKey="Garcia Orr N, Jose C" sort="Garcia Orr N, Jose C" uniqKey="Garcia Orr N J" first="José C." last="García-Borr N">José C. García-Borr N</name></noRegion><name sortKey="Jimenez Ervantes, Celia" sort="Jimenez Ervantes, Celia" uniqKey="Jimenez Ervantes C" first="Celia" last="Jiménez-Cervantes">Celia Jiménez-Cervantes</name><name sortKey="Sanchez Aorden, Berta L" sort="Sanchez Aorden, Berta L" uniqKey="Sanchez Aorden B" first="Berta L." last="Sánchez-Laorden">Berta L. 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