LPAR6 explained

Lysophosphatidic acid receptor 6, also known as LPA₆, P2RY5 and GPR87, is a protein that in humans is encoded by the LPAR6 gene.^{[1] [2] [3]} LPA₆ is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).^{[4] [5]}

The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation.^[6]

Role in hair growth/loss

In February 2008, researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss, opening a broad path to treatments for baldness. They found that mutations in the gene P2RY5 causes a rare, inherited form of hair loss called hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth. The fact that any receptor plays a specific role in hair growth was previously unknown to scientists, and with this new knowledge a focus on finding more of these genes may be able to lead to therapies for many different types of hair loss.^{[4] [7]}

In 2013, it was found that mutations in LPAR6 give rise to the Cornish Rex cat breed, which has a form of ectodermal dysplasia characterised by short woolly hair which is susceptible to loss.^[8]

See also

• Lysophospholipid receptor
• P2Y receptor

Further reading

• Toguchida J, McGee TL, Paterson JC, etal . Complete genomic sequence of the human retinoblastoma susceptibility gene. . Genomics . 17 . 3 . 535–43 . 1993 . 7902321 . 10.1006/geno.1993.1368 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Herzog H, Darby K, Hort YJ, Shine J . Intron 17 of the human retinoblastoma susceptibility gene encodes an actively transcribed G protein-coupled receptor gene. . Genome Res. . 6 . 9 . 858–61 . 1997 . 8889552 . 10.1101/gr.6.9.858 . free .
• Li Q, Schachter JB, Harden TK, Nicholas RA . The 6H1 orphan receptor, claimed to be the p2y5 receptor, does not mediate nucleotide-promoted second messenger responses. . Biochem. Biophys. Res. Commun. . 236 . 2 . 455–60 . 1997 . 9240460 . 10.1006/bbrc.1997.6984 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Dunham A, Matthews LH, Burton J, etal . The DNA sequence and analysis of human chromosome 13. . Nature . 428 . 6982 . 522–8 . 2004 . 15057823 . 2665288 . 10.1038/nature02379 . 2004Natur.428..522D .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Ihara H, Hirukawa K, Goto S, Togari A . ATP-stimulated interleukin-6 synthesis through P2Y receptors on human osteoblasts. . Biochem. Biophys. Res. Commun. . 326 . 2 . 329–34 . 2005 . 15582581 . 10.1016/j.bbrc.2004.11.037 .

Notes and References

1. Adrian K, Bernhard MK, Breitinger HG, Ogilvie A . Expression of purinergic receptors (ionotropic P2X1-7 and metabotropic P2Y1-11) during myeloid differentiation of HL60 cells . Biochim Biophys Acta . 1492 . 1 . 127–38 . Sep 2000 . 11004484 . 10.1016/S0167-4781(00)00094-4.
2. Ralevic V, Burnstock G . Receptors for purines and pyrimidines . Pharmacol Rev . 50 . 3 . 413–92 . Nov 1998 . 9755289 .
3. Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S . Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6 . J Biol Chem . 284 . 26 . 17731–41 . Jun 2009 . 19386608 . 2719412 . 10.1074/jbc.M808506200 . free .
4. Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC . G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth . Nat. Genet. . 40 . 3 . 329–34 . March 2008 . 18297070 . 10.1038/ng.84 . 20241237 .
5. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J . January 2010 . LPA Receptors: Subtypes and Biological Actions . Annual Review of Pharmacology and Toxicology . 50 . 1 . 157–186 . 10.1146/annurev.pharmtox.010909.105753 . 20055701.
6. Web site: Entrez Gene: P2RY5 purinergic receptor P2Y, G-protein coupled, 5.
7. Web site: Hypotrichosis simplex - About the Disease - Genetic and Rare Diseases Information Center . 2023-05-06 . rarediseases.info.nih.gov . en.
8. Gandolfi. Barbara. Alhaddad. Hasan. Affolter. Verena K.. Brockman. Jeffrey. Haggstrom. Jens. Joslin. Shannon E. K.. Koehne. Amanda L.. Mullikin. James C.. Outerbridge. Catherine A.. 2013-06-27. To the Root of the Curl: A Signature of a Recent Selective Sweep Identifies a Mutation That Defines the Cornish Rex Cat Breed. PLOS ONE. 8. 6. e67105. 10.1371/journal.pone.0067105. 1932-6203. 3694948. 23826204. 2013PLoSO...867105G. free.