Letter abstract
Nature Genetics 40, 329 - 334 (2008)
Published online: 24 February 2008 | doi:10.1038/ng.84
G protein–coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth
Sandra M Pasternack1, Ivar von Kügelgen2, Khalid Al Aboud3, Young-Ae Lee4,5, Franz Rüschendorf5, Katrin Voss6, Axel M Hillmer7, Gerhard J Molderings2, Thomas Franz8, Alfredo Ramirez9,10,11, Peter Nürnberg11,12, Markus M Nöthen1,7 & Regina C Betz1
Abstract
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-
-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.
- Institute of Human Genetics, University of Bonn, Bonn 53111, Germany.
- Department of Pharmacology, University of Bonn, Bonn 53113, Germany.
- Department of Dermatology, King Faisal Hospital, Makkah 5592, Saudi Arabia.
- Department of Pediatric Pneumology and Immunology, Charité, Humboldt-University Berlin 13353, Berlin, Germany.
- Max Delbrück Center for Molecular Medicine, Berlin 13092, Germany.
- Department of Human Genetics, University of Würzburg, Würzburg 97074, Germany.
- Department of Genomics, Life and Brain Center, University of Bonn, Bonn 53127, Germany.
- Department of Anatomy, University of Bonn, Bonn 53115, Germany.
- Institute for Genetics, University of Cologne, Cologne 50674, Germany.
- Institute of Human Genetics, University of Cologne, Cologne 50931, Germany.
- Center for Molecular Medicine Cologne, University of Cologne, Cologne 50931, Germany.
- Cologne Center for Genomics, University of Cologne, Cologne 50674, Germany.
Correspondence to: Regina C Betz1 e-mail: regina.betz@uni-bonn.de
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