AVPR2

Cilia effects upon perturbation of AVPR2

Loss-of-function effect:

No effect

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-4.27) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Phenotypes

Human ciliopathy phenotype:

nephrogenic diabetes insipidus; diabetes insipidus; Autosomal dominant polycystic kidney disease; hepatorenal syndrome; Central diabetes insipidus

Ciliopathy associations

• Polycystic Kidney Disease

Subcellular localization

cilia

Functional category

• Motile cilium & axoneme; Signaling (Hedgehog, GPCRs, ion channels)

Function

Vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific effect independent of V2R or verapamil-sensitive calcium channels. Live-imaging of single cilia shows that V2R activation increases cilioplasmic and cytoplasmic cAMP levels, whereas tolvaptan mediates cAMP changes only in a cilia-specific manner(PMID: 31024067).