ADGRG6 Membrane Protein Introduction

Introduction of ADGRG6

ADGRG6, also known as developmentally regulated G-protein-coupled receptor (DREG) or G-protein coupled receptor 126 (GPR126), is a protein encoded by the ADGRG6 gene. As a member of the adhesion G protein-coupled receptor (aGPCR) family, ADGRG6 contains a seven-transmembrane domain and a long N-terminal region rich in functional motifs.

Function of ADGRG6 Membrane Protein

During the past years, ADGRG6 has been widely studied. As a member of the adhesion GPCR family, it is extensively expressed on stromal cells and involved in cell-cell or cell-matrix adhesion. Studies have shown that ADGRG6 is associated with adult height, more specially trunk height, pulmonary function,and adolescent idiopathic scoliosis. It has been also reported that ADGRG6 is an evolutionarily conserved regulator of myelination. During development, ADGRG6 is thought to regulate cAMP concentration in SCs via interactions with G-proteins, and elevating cAMP in SCs upregulates the expression of myelin-related molecules. What’s more, ADGRG6 is required in multiple tissues during development including in the endocardium for normal heart development in the mouse, in Schwann cells for myelination of peripheral axons in zebrafish and in mouse and for inner ear development in zebrafish. And, ADGRG6 could stimulate VEGF signaling and angiogenesis by modulating VEGF receptor 2 (VEGFR2) expression through STAT5 and GATA2 in endothelial cells.

Fig.1 Adhesion GPCRs as Novel Actors in Neural and Glial Cell Functions. (Sigoillot, et.al. 2016)

Application of ADGRG6 Membrane Protein in Literature

1. Liu G, et.al. Genetic polymorphisms of GPR 126 are functionally associated with PUMC classifications of adolescent idiopathic scoliosis in a Northern Han population. Journal of cellular and molecular medicine. 2018, 22(3): 1964-71. PubMed ID: 29363878

This article reveals that locus of ADGRG6 is significantly associated with disease in northern Chinese Han Adolescent Idiopathic Scoliosis patients. The SNPs rs225694 and rs2294773 are associated with different AIS PUMC classifications.

2. Mogha A, et.al. Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair. Journal of Neuroscience. 2016, 36(49): 12351-67. PubMed ID: 27927955

This article reveals that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury.

3. Küffer A, et.al. The prion protein is an agonistic ligand of the G protein-coupled receptor Adgrg6. Nature. 2016, 536(7617): 464. PubMed ID: 27501152

This article suggests that the cellular prion protein PrP(C) could promote myelin homeostasis through flexible tail-mediated Gpr126 agonism. And these observations are relevant to the pathogenesis of demyelinating polyneuropathies-common debilitating diseases for which there are limited therapeutic options.

4. Karner CM, et.al. Gpr126/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus excavatum in mice. Human molecular genetics. 2015, 24(15): 4365-73. PubMed ID: 25954032

This article indicates that Gpr126 may be a genetic cause for the pathogenesis of AIS and PE in a mouse model.

5. Kitagaki J, et.al. A putative association of a single nucleotide polymorphism in GPR126 with aggressive periodontitis in a Japanese population. PloS one. 2016, 11(8): e0160765. PubMed ID: 27509131

This report reveals that GPR126 might be important in maintaining the homeostasis of periodontal ligament tissues through regulating the cytodifferentiation of HPDL cells. The GPR126SNP rs536714306 negatively influences this homeostasis, leading to the development of AgP, which indicates that it is a candidate genetic risk factor for AgP in the Japanese population

ADGRG6 Preparation Options

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Reference

1. Sigoillot, et al. (2016). Adhesion GPCRs as Novel Actors in Neural and Glial Cell Functions: From Synaptogenesis to Myelination. Handb Exp Pharmacol. 234, 275-298.

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