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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/ng.84 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Frequency locked whispering evanescent resonator (FLOWER) for biochemical sensing applications.
Nat Protoc
January 2025
Wyant College of Optical Sciences, The University of Arizona, Tucson, AZ, USA.
Sensitive, rapid and label-free biochemical sensors are needed for many applications. In this protocol, we describe biochemical detection using FLOWER (frequency locked optical whispering evanescent resonator)-a technique that we have used to detect single protein molecules in aqueous solution as well as exosomes, ribosomes and low part-per-trillion concentrations of volatile organic compounds. Whispering gallery mode microtoroid resonators confine light for extended time periods (hundreds of nanoseconds).
View Article and Find Full Text PDFLGR4 is essential for maintaining β-cell homeostasis through suppression of RANK.
Mol Metab
January 2025
Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA 91010, USA; Department of Translational Research and Cellular Therapeutics, City of Hope, Duarte, CA 91010, USA. Electronic address:
Objective: Loss of functional β-cell mass is a major cause of diabetes. Thus, identifying regulators of β-cell health is crucial for treating this disease. The In this study, we assessed the regulation of Lgr4 in islets, and the role of LGR4 and LGR4/RANK stoichiometry in β-cell health under basal and stress-induced conditions, in vitro and in vivo.
View Article and Find Full Text PDFChronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.
Mol Metab
January 2025
Section of Endocrinology and Investigative Medicine, Imperial College London, United Kingdom. Electronic address:
Objective: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.
View Article and Find Full Text PDFShenghui decoction inhibits neuronal cell apoptosis to improve Alzheimer's disease through the PDE4B/cAMP/CREB signaling pathway.
Phytomedicine
January 2025
Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan Province, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China; Collaborative Innovation Center of Research and Development on the whole Industry Chain of Yu-Yao, Henan University of Chinese Medicine, Zhengzhou 450046, Henan, China. Electronic address:
Background: Shenghui Decoction (SHD) is a frequently utilized traditional Chinese medicine formula in clinical settings for addressing cognitive impairment in elderly individuals. Nevertheless, the precise mechanism by which SHD exerts its effects on the most prevalent form of dementia, Alzheimer's disease (AD), remains to be elucidated.
Methods: Temperature-induced transgenic C.
G-protein-coupled estrogen receptor 30 regulation of signaling downstream of protein kinase Cε mediates sex dimorphism in hyaluronan-induced antihyperalgesia.
Pain
October 2024
Department of Oral and Maxillofacial Surgery, UCSF Pain and Addiction Research Center, University of California at San Francisco, San Francisco, California.
High molecular weight hyaluronan (HMWH) inhibits hyperalgesia induced by diverse pronociceptive inflammatory mediators and their second messengers, in rats of both sexes. However, the hyperalgesia induced by ligands at 3 pattern recognition receptors, lipopolysaccharide (a toll-like receptor 4 agonist), lipoteichoic acid (a toll-like receptor 2/6 agonist), and nigericin (a NOD-like receptor family, pyrin domain containing 3 activator), and oxaliplatin and paclitaxel chemotherapy-induced peripheral neuropathy are only attenuated in males. After gonadectomy or intrathecal administration of an antisense to G-protein-coupled estrogen receptor 30 (GPER) mRNA, HMWH produces antihyperalgesia in females.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!