G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth

被引：323

作者：

Pasternack, Sandra M. ^{[1
,2
]}

von Kuegelgen, Ivar

Al Aboud, Khalid ^{[3
]}

Lee, Young-Ae ^{[4
,5
]}

Rueschendorf, Franz ^{[5
]}

Voss, Katrin ^{[6
]}

Hillmer, Axel M. ^{[7
]}

Molderings, Gerhard J. ^{[2
]}

Franz, Thomas ^{[8
]}

Ramirez, Alfredo ^{[9
,10
,11
]}

Nuernberg, Peter ^{[11
,12
]}

Noethen, Markus M. ^{[1
,7
]}

Betz, Regina C. ^{[1
]}

机构：

[1] Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany

[2] Univ Bonn, Dept Pharmacol, D-53113 Bonn, Germany

[3] King Faisal Hosp, Dept Dermatol, Mecca 5592, Saudi Arabia

[4] Humboldt Univ, Charite, Dept Pediat Pneumol & Immunol, D-13353 Berlin, Germany

[5] Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany

[6] Univ Wurzburg, Dept Human Genet, D-97074 Wurzburg, Germany

[7] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany

[8] Univ Bonn, Dept Anat, D-53115 Bonn, Germany

[9] Univ Cologne, Inst Genet, D-50674 Cologne, Germany

[10] Univ Cologne, Inst Human Genet, D-50931 Cologne, Germany

[11] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany

[12] Univ Cologne, Cologne Ctr Genom, D-50674 Cologne, Germany

来源：

NATURE GENETICS | 2008年 / 40卷 / 03期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1038/ng.84

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：329 / 334

页数：6

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