Melanocortin MC₁ receptor in human genetics and model systems.
Melanocortin MC₁ receptor in human genetics and model systems.
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DOI：
10.1016/j.ejphar.2010.11.040
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发表时间：
2011-06-11
影响因子：
5
通讯作者：
Sturm, Richard A.
中科院分区：
文献类型：
--
作者：
Beaumont, Kimberley A.;Wong, Shu S.;Ainger, Stephen A.;Liu, Yan Yan;Patel, Mira P.;Millhauser, Glenn L.;Smith, Jennifer J.;Alewood, Paul F.;Leonard, J. Helen;Sturm, Richard A.
黑素皮质素MC1受体是一种G蛋白偶联受体，在皮肤和头发的黑色素细胞中表达，在调节人类色素沉着中起关键作用。紫外线照射后，黑素皮质素MC1受体激活导致皮肤黑素细胞内从红/黄黑色素到棕色/黑色真黑色素合成的转换；然后这种色素被转移到皮肤周围的角质形成细胞。黑色素成熟和吸收的增加导致皮肤晒黑，为皮肤细胞提供物理保护，使其免受紫外线辐射引起的DNA损伤。黑素皮质素mc1受体多态性在高加索人群中普遍存在，一些变异等位基因与红发色、白皙皮肤、晒黑效果差和皮肤癌风险增加有关。在这里，我们将讨论使用小鼠毛色模型、人类遗传关联研究和体外细胞培养研究来确定黑素皮质素MC1受体的复杂功能，以及黑素皮质素MC1受体变异等位基因与红色发色表型之间关联的分子机制。最近的研究表明，黑素皮质素MC1受体具有许多非色素功能，并且黑素皮质素MC1受体变异等位基因所带来的皮肤癌风险增加在一定程度上与色素沉着表型无关。使用新的转基因小鼠模型，研究新的黑素皮质素MC1受体反应基因，以及使用更先进的人体皮肤模型，如3D皮肤重建，可能为理解人类黑素皮质素MC1受体多态性的药物遗传学提供关键要素。
The melanocortin MC1 receptor is a G -protein coupled receptor expressed in melanocytes of the skin and hair and is known for its key role in regulation of human pigmentation. Melanocortin MC1 receptor activation after ultraviolet radiation exposure results in a switch from the red/yellow pheomelanin to the brown/black eumelanin pigment synthesis within cutaneous melanocytes; this pigment is then transferred to the surrounding keratinocytes of the skin. The increase in melanin maturation and uptake results in tanning of the skin, providing a physical protection of skin cells from ultraviolet radiation induced DNA damage. Melanocortin MC 1 receptor polymorphism is widespread within the Caucasian population and some variant alleles are associated with red hair colour, fair skin, poor tanning and increased risk of skin cancer. Here we will discuss the use of mouse coat colour models, human genetic association studies, and in vitro cell culture studies to determine the complex functions of the melanocortin MC1 receptor and the molecular mechanisms underlying the association between melanocortin MC1 receptor variant alleles and the red hair colour phenotype. Recent research indicates that melanocortin MC1 receptor has many non-pigmentary functions, and that the increased risk of skin cancer conferred by melanocortin MC1 receptor variant alleles is to some extent independent of pigmentation phenotypes. The use of new transgenic mouse models, the study of novel melanocortin MC1 receptor response genes and the use of more advanced human skin models such as 3D skin reconstruction may provide key elements in understanding the pharmacogenetics of human melanocortin MC1 receptor polymorphism .
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影响因子：
64.5
作者：
Cui, Rutao;Widlund, Hans R.;Fisher, David E.
通讯作者：
Fisher, David E.
影响因子：
3.5
作者：
Flanagan, N;Healy, E;Rees, JL
通讯作者：
Rees, JL
影响因子：
4.8
作者：
Bellei, Barbara;Maresca, Vittoria;Picardo, Mauro
通讯作者：
Picardo, Mauro
影响因子：
6.5
作者：
Duffy, David L.;Zhao, Zhen Z.;Sturm, Richard A.;Hayward, Nicholas K.;Martin, Nicholas G.;Montgomery, Grant W.
通讯作者：
Montgomery, Grant W.
影响因子：
9.8
作者：
Bastiaens, MT;ter Huurne, JAC;Bavinck, NJB
通讯作者：
Bavinck, NJB