Loss of function mutations of the human melanocortin 1 receptor are common and are associated with red hair

Biochemical and Biophysical Research Communications
Helgi B SchiöthJonathan L Rees

Abstract

The melanocortin 1 receptor is a G-protein-coupled receptor that acts as a control point for control of the eumelanin/phaeomelanin ratio in mouse hair. MC1 receptor loss of function mutations lead to an increase in the ratio of phaeomelanin/eumelanin in many mammals resulting in yellow or red coat colours. We have previously shown that several common point mutations in the human MC1 receptor are overrepresented in North European redheads and in individuals with pale skin. In order to determine the functional significance of these changes we have carried out transfection and binding studies. Expression of the Val60Leu, Arg142His, Arg151Cys, Arg160Trp, and Asp294His receptors in COS 1 cells revealed that these receptors were unable to stimulate cAMP production as strongly as the wild type receptor in response to alpha-melanocyte-stimulating hormone stimulation. None of the mutant receptors displayed complete loss of alphaMSH binding, with only the Arg142His and Asp294His displaying a slight reduction in binding affinity.

References

Mar 26, 2003·European Journal of Biochemistry·Maria K LingHelgi B Schiöth
Jul 28, 2004·Anesthesiology·Edwin B LiemDaniel I Sessler
Feb 20, 2008·Photochemistry and Photobiology·Márta SzéllLajos Kemény
Mar 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey S MogilRoger B Fillingim
Aug 10, 2005·Proceedings. Biological Sciences·Nicholas I Mundy
May 16, 2012·Journal of the American Academy of Dermatology·Katherine A WardMaria K Hordinsky
Dec 15, 2007·The Journal of Investigative Dermatology·Tomonori MotokawaTakayuki Katagiri
Jul 6, 2010·Mutation Research·Dominique Scherer, Rajiv Kumar
Jun 23, 2009·General and Comparative Endocrinology·E SánchezJ M Cerdá-Reverter
Mar 10, 2009·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Gilli Galore-HaskelEitan Friedman
Feb 17, 2001·The Journal of Investigative Dermatology·N F BoxRichard A Sturm
Apr 29, 2006·The Journal of Investigative Dermatology·Muriel LiboutetNadem Soufir
Jul 4, 2003·The Journal of Investigative Dermatology·Colin A McKenzieJonathan L Rees
Jan 19, 2006·The Journal of Investigative Dermatology·Berta L Sánchez-LaordenCelia Jiménez-Cervantes
Dec 21, 2007·The Journal of Investigative Dermatology·Stéphane F CommoBruno A Bernard
Sep 22, 2007·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Guiling DunLanhui Li
Nov 10, 2004·Photodermatology, Photoimmunology & Photomedicine·Eugene Healy
Jul 15, 2004·Pigment Cell Research·Jesús Sánchez-MásCelia Jiménez-Cervantes
Sep 3, 2003·Pigment Cell Research·Jesús Sánchez MásJosé C García-Borrón
Jul 10, 2003·Annals of the New York Academy of Sciences·Janis AncansAnthony J Thody
Jul 10, 2003·Annals of the New York Academy of Sciences·Richard A SturmN G Martin
Jul 9, 2009·International Journal of Cancer. Journal International Du Cancer·Dominique SchererRajiv Kumar
Mar 27, 2009·Experimental Dermatology·M Laurin CouncilAnne M Bowcock
Feb 7, 2007·Human Mutation·Meg R GerstenblithMaria Teresa Landi
Mar 28, 2008·International Journal of Cancer. Journal International Du Cancer·Sara RaimondiMaria Concetta Fargnoli
Nov 11, 2005·Pigment Cell Research·José C García-BorrónCelia Jiménez-Cervantes
Mar 21, 2007·Pigment Cell Research·Tomonori MotokawaTakayuki Katagiri
Nov 7, 2006·Pigment Cell Research·Francisco SolanoGhanem Ghanem
Aug 8, 2008·Human Mutation·Mickaël GuedjMelanCohort Investigators

Related Concepts

Transfection
ACTH (1-13)NH2
MC1R Protein
Second messenger
COS-7 Cells
Corticotropin Receptors
Homologous Sequences, Amino Acid
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Mouse hair antigen

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