| Title: |
Constitutive Gαi Coupling Activity of Very Large G Proteincoupled Receptor 1 (VLGR1) and Its Regulation by PDZD7 Protein. |
| Authors: |
Qiao-Xia Hu1, Jun-Hong Dong2,3, Hai-Bo Du4, Dao-Lai Zhang1,5, Hong-Ze Ren4, Ming-Liang Ma1, Yuan Cai6, Tong-Chao Zhao1, Xiao-Lei Yin4, Xiao Yu2, Tian Xue6, Zhi-Gang Xu4 xuzg@sdu.edu.cn, Jin-Peng Sun1 sunjinpeng@sdu.edu.cn |
| Source: |
Journal of Biological Chemistry. 8/29/2014, Vol. 289 Issue 35, p24215-24225. 11p. |
| Subject Terms: |
*G protein coupled receptors, *G protein genetics, *HAIR cell regeneration, *T cells, *T cell receptors, *PHYSIOLOGY |
| Abstract: |
The very largeGprotein-coupled receptor 1 (VLGR1) is a core component in inner ear hair cell development. Mutations in the vlgr1 gene cause Usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. However, the mechanism of VLGR1-regulated intracellular signaling and its role in Usher syndrome remain elusive. Here, we show that VLGR1 is processed into two fragments after autocleavage at the G protein-coupled receptor proteolytic site. The cleaved VLGR1 β-subunit constitutively inhibited adenylate cyclase (AC) activity through Gαi coupling. Co-expression of the Gαiq chimera with the VLGR1 β-subunit changed its activity to the phospholipase C/nuclear factor of activated T cells signaling pathway, which demonstrates the Gαi protein coupling specificity of this subunit. An R6002A mutation in intracellular loop 2 of VLGR1 abolished Gαi coupling, but the pathogenic VLGR1 Y6236fsx1 mutant showed increased AC inhibition. Furthermore, overexpression of another Usher syndrome protein, PDZD7, decreased the AC inhibition of the VLGR1 β-subunit but showed no effect on the VLGR1 Y6236fsx1 mutant. Taken together, we identified an independentG αi signaling pathway of the VLGR1β-subunit and its regulatory mechanisms that may have a role in the development of Usher syndrome. [ABSTRACT FROM AUTHOR] |
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