G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth.
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.
Pasternack
Sandra M
SM
Institute of Human Genetics, University of Bonn, Bonn 53111, Germany.
von Kügelgen
Ivar
I
Al Aboud
Khalid
K
Lee
Young-Ae
YA
Rüschendorf
Franz
F
Voss
Katrin
K
Hillmer
Axel M
AM
Molderings
Gerhard J
GJ
Franz
Thomas
T
Ramirez
Alfredo
A
Nürnberg
Peter
P
Nöthen
Markus M
MM
Betz
Regina C
RC
D000328:Adult; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005190:Family; D006197:Hair / Q000254:growth & development*; D006801:Humans; D007039:Hypotrichosis / Q000235:genetics*; D008246:Lysophospholipids / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D010375:Pedigree; D010802:Phylogeny; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D049368:Receptors, Lysophosphatidic Acid
D008246:Lysophospholipids; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; C082320:LPAR4 protein, human; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid