Signaling modification by GPCR heteromer and its implication on X-linked nephrogenic diabetes insipidus

Hans K.H. Ng, Kaleeckal G. Harikumar, Laurence J. Miller, Billy K.C. Chow

Research output: Contribution to journalArticle

Abstract

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 Vpmediated 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.

Original languageEnglish (US)
Article numbere0163086
JournalPloS one
Volume11
Issue number9
DOIs
StatePublished - Sep 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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