G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth
G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth
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DOI：
10.1038/ng.84
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发表时间：
2008-03-01
期刊：
影响因子：
30.8
通讯作者：
Betz, Regina C.
中科院分区：
文献类型：
--
作者：
Pasternack, Sandra M.;von Kuegelgen, Ivar;Betz, Regina C.
单纯性毛少症是一组非综合征性的人类脱发。我们将这种疾病的常染色体隐性形式定位到染色体13q14.11-13q21.33上，并在编码孤儿G蛋白偶联受体的P2RY5上发现了纯合截断突变。此外，我们在报告基因和放射配体结合实验中发现了一种生物活性脂质油基-l - α -溶血磷脂酸（LPA）作为P2Y5的配体。同源性和信号转导途径研究表明，P2Y5是LPA受体亚群的成员，该亚群还包括LPA4和LPA5。我们的研究首次表明，G蛋白偶联受体对于维持人类头发生长至关重要。这一发现可能为治疗人类脱发提供新的治疗方法。
Hypotrichosis simplex is a group of nonsyndromic human alopecias. We mapped an autosomal recessive form of this disorder to chromosome 13q14.11-13q21.33, and identified homozygous truncating mutations in P2RY5, which encodes an orphan G protein-coupled receptor. Furthermore, we identified oleoyl-L-alpha-lysophosphatidic acid (LPA), a bioactive lipid, as a ligand for P2Y5 in reporter gene and radioligand binding experiments. Homology and studies of signaling transduction pathways suggest that P2Y5 is a member of a subgroup of LPA receptors, which also includes LPA4 and LPA5. Our study is the first to implicate a G protein-coupled receptor as essential for and specific to the maintenance of human hair growth. This finding may provide opportunities for new therapeutic approaches to the treatment of hair loss in humans.