HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.06-5922fjev1 20/11/1927    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rouzaud, F. Articles by Hearing, V. J. Search for Related Content PubMed PubMed Citation Articles by Rouzaud, F. Articles by Hearing, V. J.

Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms

Francois Rouzaud^*,,1, Gertrude-E. Costin^*, Yuji Yamaguchi^*, Julio C. Valencia^*, Werner F. Berens^*, Kevin G. Chen^*, Toshihiko Hoashi^*, Markus Böhm, Zalfa A. Abdel-Malek^¶ and Vincent J. Hearing^*

^* Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA;

Department of Medicinal Chemistry, University of Florida, Gainesville, Florida, USA;

Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Munster, Germany; and

^¶ Department of Dermatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

¹Correspondence: University of Florida, Department of Medicinal Chemistry, Rm. P5–26, 1600 SW Archer Rd., Gainesville, FL 32610, USA. E-mail: frouzaud{at}ufl.edu

ABSTRACT

Melanin synthesized by epidermal melanocytes protects the skin against UVR-induced DNA damage and skin cancer. Exposure to UVR increases the synthesis of the photoprotective eumelanin on activation of MC1R, a melanoma susceptibility gene. We studied the expression of MC1R under UVR and -MSH stimulation in skin of different ethnic origins and in melanocytes of various pigmentary levels. This study identifies and characterizes a novel MC1R isoform (MC1R350) generated by alternative splicing of the classically known MC1R (MC1R317). We demonstrate that the melanin content of melanocytes shows a significant positive correlation with MC1R317 levels but correlates inversely with the amount of MC1R350, suggesting that this latter isoform could act as a negative regulator of melanin synthesis. We confirmed that hypothesis by showing that while MC1R317 signaling significantly increases the expression of MITF and tyrosinase, two key factors in the melanin synthesis pathway, MC1R350 dramatically hampers their expression. In the skin, we show that UVR does not increase MC1R350 expression but does significantly increase MC1R317. Taken together, our results strongly suggest that MC1R350 acts as a negative regulator of skin pigmentation and demonstrate for the first time that MC1R isoform-specific expression is closely related to skin pigmentation and photoprotection.—Rouzaud, F., Costin, G-E., Yamaguchi, Y., Valencia, J. C., Berens, W. F., Chen, K. G., Hoashi, T., Böhm, M., Abdel-Malek, Z. A., Hearing, V. J. Regulation of constitutive and UVR-induced skin pigmentation by melanocortin 1 receptor isoforms.

This article has been cited by other articles:

				Y. Yamaguchi, M. Brenner, and V. J. Hearing The Regulation of Skin Pigmentation J. Biol. Chem., September 21, 2007; 282(38): 27557 - 27561. [Full Text] [PDF]

				T. Haitina, A. Ringholm, J. Kelly, N. I. Mundy, and H. B. Schioth High Diversity in Functional Properties of Melanocortin 1 Receptor (MC1R) in Divergent Primate Species Is More Strongly Associated with Phylogeny than Coat Color Mol. Biol. Evol., September 1, 2007; 24(9): 2001 - 2008. [Abstract] [Full Text] [PDF]