Open AccessSignaling Modification by GPCR Heteromer and Its Implication on X-Linked Nephrogenic Diabetes Insipidus
Author(s) -
Hans K. H. Ng,
Kaleeckal G. Harikumar,
Laurence J. Miller,
Billy K. C. Chow
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0163086
Subject(s) - nephrogenic diabetes insipidus , aquaporin 2 , arginine vasopressin receptor 2 , reabsorption , vasopressin , g protein coupled receptor , diabetes insipidus , medicine , microbiology and biotechnology , endocrinology , kidney , homeostasis , receptor , biology , mechanical engineering , antagonist , water channel , engineering , inlet
The involvement of secretin (SCT) and secretin receptor (SCTR) in regulating body water homeostasis is well established. Identified as one of the vasopressin (Vp)-independent mechanisms in fluid balance, SCT regulates aquaporin 2 (AQP2) in the kidney distal collecting duct cells through activating intracellular cAMP production. This ability to bypass Vp-mediated water reabsorption in kidney implicates SCT’s potential to treat nephrogenic diabetes insipidus (NDI). Research on NDI in the past has largely been focused on the searching for mutations in vasopressin receptor 2 (AVPR2), while the functional relationship between SCTR, AVPR2 and NDI remains unclear. Here, we demonstrate the interaction between SCTR and AVPR2 to modulate cellular signaling in vitro . Interestingly, we show in this report that upon heteromer formation with SCTR, R137H, a NDI-causing AVPR2 mutant that is defective in trafficking to cell surface, can functionally be rescued. Our data may provide an explanation for this clinically mild case of NDI, and insights into the pathological development of NDI in the future.