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

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-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.

Rho/ROCK pathway is essential to the expansion, differentiation, and morphological rearrangements of human neural stem/progenitor cells induced by lysophosphatidic acid

“…Similarly, an increase of ATX mRNA expression was observed in both noggin-treated cells and neurospheres. LPA 3 and LPA 5 mRNA were downregulated upon neural differentiation, and no signifi cant modulation was observed for LPA 2 and LPA 4 . Very low levels of sPLA 2 were observed at all stages of differentiation.…”

“…1 ). All of the undifferentiated and the differentiated hPSCs expressed LPA [1][2][3][4][5] , ATX , and sPLA 2 mRNA ( Fig. 1 ), with LPA 2 and…”

“…1E, F ). Given the similar trend of expression of LPA [1][2][3][4][5] , ATX , and sPLA 2 mRNA in neurospheres from the two clones of iPSCs, we assessed most biological effects of LPA in iPS1 and compared them with hESCs. LPA 4 mRNA being the most abundant.…”

“…A negative control ( Ϫ RT) consisting in the absence of reverse transcriptase was performed to check the absence of genomic DNA. qPCR was carried out using TaqMan Universal master mix (Applied Biosystems) and the 7900HT Fast Real-Time PCR system (Applied Biosystems) and TaqMan gene expression assays for LPA [1][2][3][4][5] and ATX (Applied Biosystems). TaqMan gene expression assays for LPA 1 (Hs00173500_m1), LPA 2 (Hs00173704_m1), LPA 3 (Hs00173857_m1), LPA 4 (Hs00271072_s1), LPA 5 (Hs01051307_ m1), ATX (Hs00196470_m1), PLA2-group IIA (Hs00179898_ m1), ROCK1 (Hs01127699_m1), and ROCK2 (Hs00178154_m1) were used (Applied Biosystems).…”

Expression patterns of the lysophospholipid receptor genes during mouse early development

“…Some are expressed at or near important local signaling centers such as the rostral forebrain, the ZLI, and the MHB, suggesting that lysophospholipid signaling might interact with well-documented developmental signaling pathways such as those of FGF, BMP, Wnt, and Shh in brain development. Recently, a number of additional LPA receptor genes belonging to the G protein-coupled P2Y receptor gene family have been identified, the functions of some of which have been suggested by comparison with human mutations (Tabata et al, 2007;Pasternack et al, 2008;Shimomura et al, 2008). It will be of considerable interest to explore the expression pattern and role of new genes such as Gpr87 and P2ry5 (P2y5).…”