LPAR6 Membrane Protein Introduction

Introduction of LPAR6

LPAR6, encoded by LPAR6 gene, is a member of G-protein coupled receptor family and couples to G_12/13, G_s and G_i. It is the most recently discovered LPAR subtype. LPAR6 is also known as P2Y5 because of sequence homology with P2Y receptors. The receptor is widely expressed in many human tissues, including placenta, fat, esophagus, gallbladder, prostate, urinary bladder and other 20 tissues, thus also indicating that it may possess diverse functions in the cell biological processes. It has shown that LPAR6 is associated with hypotrichosis. But most studies are required to investigate further functions of the receptor.

Function of LPAR6 Membrane Protein

LPAR6 is activated by LPA and stimulates intracellular signaling molecules actions, such as increased intracellular Ca²⁺, cAMP accumulation, and ERK1/2 activation, thereby transducing cell signaling pathway and inducing multiple cell effects. Several studies have shown that mutations in LPAR6 are associated with genetic hair loss and autosomal recessive hypotrichosis. It has been reported that lipase member H (LIPH) regulates hair follicle development by modulating epidermal growth factor receptor (EGFR) signaling pathway and LIPH mutations hypotrichosis patients are associated with decreased LPA production and reduced LPAR6 activation. These findings suggest that LPAR6 can be considered as a potential therapeutic target for hair loss. Besides, LPAR6 is involved in the progression of tumors. The study has indicated that the overexpression of LPAR6 is associated with high proliferation rates and poorer survival outcomes in hepatocellular carcinoma, thus uncovering the potential prognostic role in hepatocellular carcinoma treatment.

Fig.1 LPAR signaling and functional outcomes. (Stoddard, 2015)

Application of LPAR6 Membrane Protein in Literature

1. Takahashi K., et al. Effects of LPA1 and LPA6 on the regulation of colony formation activity in colon cancer cells treated with anticancer drugs. Journal of Receptor & Signal Transduction Research. 2018, 38(1):71-75. PubMed ID: 29369010
   
   

   The study indicates that LPA1 and LPA6 may be involved in the regulation of the colony formation activity in DLD1 cells treated with anticancer drugs.

2. Ahmad F., et al. Novel sequence variants in the LIPH and LPAR6 genes underlies autosomal recessive woolly hair/hypotrichosis in consanguineous families. Congenital Anomalies. 2018, 58(1):24-28. PubMed ID: 28425126
   
   

   The study finds a novel homozygous frameshift variant (c.68_69dupGCAT; p.Phe24Hisfs*29) in the LPAR6 gene, which is associated with autosomal recessive woolly hair/hypotrichosis in consanguineous families.

3. Takahashi K., et al. Lysophosphatidic acid (LPA) signaling via LPA4 and LPA6 negatively regulates cell motile activities of colon cancer cells. Biochem Biophys Res Commun. 2017, 483(1):652-657. PubMed ID: 27993681
   
   

   The study finds that the inhibition of LPA4 and LPA6 can increase cell motile activities of DLD1 and HCT116 cells, as well as long-term 5-FU, treated cells.

4. Sadam A., et al. Study of lysophosphatidic acid receptors (LPARs) in buffalo uterus demonstrated upregulation of LPAR1 and LPAR6 in early pregnancy. Theriogenology. 2017, 99:90-97. PubMed ID: 28708504
   
   

   The findings reveal that the higher LPA1 and LPA6 levels are found in the early-pregnant uterus, indicating their potential roles in pregnancy. And LPA6 plays a greater role in mediating LPA signaling in early pregnancy (29-42 days) of buffalo.

5. Pedurupillay C.R.J., et al. Segregation of incomplete achromatopsia and alopecia due to PDE6H and LPAR6 variants in a consanguineous family from Pakistan. Genes. 2016, 7(8):41. PubMed ID: 27472364
   
   

   The findings indicate that biallelic loss-of-function variants (c.188A>T) in the LPAR6 gene induce hypotrichosis type 8, with or without woolly hair, a form of non-syndromic alopecia.

LPAR6 Preparation Options

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Reference

1. Stoddard N C and Chun J. (2015). Promising pharmacological directions in the world of lysophosphatidic acid signaling. Biomolecules & Therapeutics, 23(1), 1-11.

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