Akademik Veri Yönetim Sistemi
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION, cilt.42, ss.573-579, 2022 (SCI-Expanded)
Loss-of-function mutations of the arginine vasopressin receptor 2 gene (AVPR2) cause Nephrogenic diabetes insipidus (NDI). AVPR2 is a kind of G protein coupled receptor (GPCR) and mainly couples with G alpha s protein leading to cAMP accumulation in the cell as a secondary messenger. Recent studies showed that some AVPR2 mutations could cause biased G alpha q/11 protein coupling rather than G alpha s. Investigation into the characterization of biased receptors may give insights into the relationship between the conformational change of the receptor because of the mutation and related downstream signaling. In this study, R68W and V162A were analyzed to whether they show a bias to G alpha s or G alpha q/11 proteins. Their functionality in terms of cAMP production via G alpha s protein coupling was decreased compared to the wild-type receptor. On the other hand, they showed the ability to couple with G alpha q/11 protein and make Ca2+ mobilization at different levels in the cell. R68W showed bias to coupling with G alpha q/11 protein rather than V162A and wild-type receptor. Studies about the G alpha protein coupling bias of mutant AVPR2s may broaden our understanding of the relationship between the changed conformation of the receptor and consequently activated signaling pathways, and also may shed light on the development of more effective new therapeutics.