LPAR6
LPAR6 (lysophosphatidic acid receptor 6, also known as P2RY5) is a G protein-coupled receptor that mediates cellular responses to lysophosphatidic acid (LPA), a bioactive lipid involved in proliferation, migration, differentiation, and tissue homeostasis[1][2]. Mechanistically, LPAR6 functions as an LPA-responsive receptor coupled to Gα_i and Gα_12/13 signaling, linking extracellular lipid signals to cytoskeletal regulation and cell-adhesion processes[1]. Through LPA-dependent signaling networks, LPAR6 contributes to physiological regulation in multiple tissues, including vascular and epithelial systems[2][5]. In disease-related studies, genetic alterations of LPAR6 have been associated with autosomal recessive hypotrichosis and woolly hair phenotypes, demonstrating an essential role in hair follicle biology and normal hair growth maintenance[3][4]. Experimental evidence further indicates that LPAR6 regulates endothelial blood-brain barrier function, supporting investigation of this receptor in models of hepatic encephalopathy and neurovascular dysfunction[2]. Compared with other LPA receptor isoforms, LPAR6 is distinguished by its strong association with hair-follicle development and inherited hair disorders, providing a biologically specific phenotype that is less characteristic of other LPA receptor family members[3][4]. For experimental applications, pharmacological inhibition of LPAR6 has been reported to suppress hepatocellular carcinoma growth and alter mitochondrial function, supporting the use of LPAR6 antagonists as research tools for studying LPA signaling and cancer-associated cellular responses[5].
Verweise:
- [1]. Lee M, et al. P2Y5 is a G(alpha)i, G(alpha)12/13 G protein-coupled receptor activated by lysophosphatidic acid that reduces intestinal cell adhesion. Am J Physiol Gastrointest Liver Physiol. 2009 Oct;297(4):G641-54. [Content Brief]
- [2]. Masago K, et al. Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy. Biochem Biophys Res Commun. 2018 Jul 2;501(4):1048-1054. [Content Brief]
- [3]. Azhar A, et al. A novel mutation in lysophosphatidic acid receptor 6 gene in autosomal recessive hypotrichosis and evidence for a founder effect. Eur J Dermatol. 2012 Jul-Aug;22(4):464-6. [Content Brief]
- [4]. Horev L, et al. A novel deletion mutation in P2RY5/LPA(6) gene cause autosomal recessive woolly hair with hypotrichosis. J Eur Acad Dermatol Venereol. 2010 Jul;24(7):858-9. [Content Brief]
- [5]. Gnocchi D, et al. Novel lysophosphatidic acid receptor 6 antagonists inhibit hepatocellular carcinoma growth through affecting mitochondrial function. J Mol Med (Berl). 2020 Feb;98(2):179-191. [Content Brief]
