Melanocytes expressing MC1R polymorphosms associated with red hair colour have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes

Roberts, Donald W., Newton, Richard A., Leonard, J. Helen and Sturm, Richard A. (2008) Melanocytes expressing MC1R polymorphosms associated with red hair colour have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes. Journal of Cellular Physiology, 215 2: 344-355. doi:10.1002/jcp.21318


Author Roberts, Donald W.
Newton, Richard A.
Leonard, J. Helen
Sturm, Richard A.
Title Melanocytes expressing MC1R polymorphosms associated with red hair colour have altered MSH-ligand activated pigmentary responses in coculture with keratinocytes
Journal name Journal of Cellular Physiology   Check publisher's open access policy
ISSN 0021-9541
Publication date 2008-05
Year available 2007
Sub-type Article (original research)
DOI 10.1002/jcp.21318
Volume 215
Issue 2
Start page 344
End page 355
Total pages 12
Place of publication Hoboken, New Jersey
Publisher Wiley
Collection year 2008
Language eng
Subject C1
270106 Cell Development (incl. Cell Division and Apoptosis)
730108 Cancer and related disorders
Abstract The occurrence of red hair and pale skin in individuals, which is associated with UV-radiation sensitivity and increased skin cancer risk, is mainly due to polymorphisms in the melanocortin-1 receptor (MC1R) expressed in melanocytes. We have established a serum free human melanocyte-keratinocyte coculture system to study the behavior and functional abilities of melanocytes expressing MC1R red hair color (RHC) variants in order to identify differences from their wild type (WT) counterparts. This model revealed the importance of elevated calcium levels in promoting strong melanocyte interaction with the surrounding keratinocytes and resulted in a dendritic melanocyte morphology similar to that in skin. However, the dendricity response following agonist activation of the MC1R receptor by NDP-MSH peptide, was markedly enhanced in WT melanocytes in comparison to RHC strains. Analysis of mRNA expression and protein levels of the major pigmentation markers following NDP-MSH treatment distinguished the enzyme dopachrome tautomerase as preferentially upregulated in cocultures of WT strains, with negligible or a much reduced response in melanocytes with RHC variant alleles. These results highlight the use of the coculture system in determining fundamental differences in the physiology of melanocytes expressing RHC MC1R receptors and those of WT genotype, which are likely to contribute to the increased skin cancer risk for individuals that carry these variants. J. Cell. Physiol. 215: 344-355, 2008. © 2007 Wiley-Liss, Inc.
Q-Index Code C1
Q-Index Status Confirmed Code

 
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