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. 2016 Nov 28;7:13636. doi: 10.1038/ncomms13636

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Copyright © 2016, The Author(s)

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Wnt5a activates intracellular calcium in the presence of Fzd receptors¹⁹. Calcium-binding protein calmodulin (CaM) and calmodulin-mimicking protein AA stimulate calcineurin. Calcineurin alters AQP2 phosphorylation at S261 and S269 leading to the apical membrane trafficking of AQP2. Additionally, calcineurin increases AQP2 mRNA expression. On the other hand, vasopressin (AVP) binding to V2R increases intracellular cAMP concentration and activates PKA. cAMP upregulates AQP2 mRNA expression, and PKA along with other basophilic kinases alters AQP2 phosphorylation at S256, S261, and S269. Wnt5a activates AQP2 by different mechanisms of the vasopressin signalling pathway. Slight inhibitory effects of H89 on Wnt5a were also observed (Fig. 4e), suggesting the existence of crosstalk between Wnt5a signalling pathway and PKA.