ArticleJournal of the American Society of Nephrology : JASN2014
A protein kinase A-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular mechanism of p-Coumaric acid in the regulation of AQP2 function through the activation of calcium-sensing receptor signaling.Scientific reports · 2026Article
- Functional Coupling of Calcium-Sensing Receptor and Polycystin-2 in Renal Epithelial Cells: Physiological Role and Potential Therapeutic Target in Polycystic Kidney Disease.International journal of molecular sciences · 2025Article
- Mechanistic complement of autosomal dominant polycystic kidney disease: the role of aquaporins.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Collecting duct water permeability inhibition by EGF is associated with decreased cAMP, PKA activity, and AQP2 phosphorylation at SerAmerican journal of physiology. Renal physiology · 2024Article
- Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease.International journal of molecular sciences · 2022Review
- Role of protein phosphatase 2A in kidney disease (Review).Experimental and therapeutic medicine · 2021Review
- Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor.Scientific reports · 2021Article
- Vasopressin receptor 2 mutations in the nephrogenic syndrome of inappropriate antidiuresis show different mechanisms of constitutive activation for G protein coupled receptors.Scientific reports · 2020Article
- Article
- Gain-of-function mutations of the V2 vasopressin receptor in nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a cell-based assay to assess constitutive water reabsorption.Pflugers Archiv : European journal of physiology · 2019Article
- Empagliflozin Contributes to Polyuria via Regulation of Sodium Transporters and Water Channels in Diabetic Rat Kidneys.Frontiers in physiology · 2019Article
- Interleukin-13 increases pendrin abundance to the cell surface in bronchial NCI-H292 cells via Rho/actin signaling.Pflugers Archiv : European journal of physiology · 2017Article
- The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment.Journal of cellular and molecular medicine · 2017Article
- Phosphatase inhibition increases AQP2 accumulation in the rat IMCD apical plasma membrane.American journal of physiology. Renal physiology · 2016Article
- Molecular mechanisms regulating aquaporin-2 in kidney collecting duct.American journal of physiology. Renal physiology · 2016Review
- EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2-Mediated Renal Water Reabsorption.Journal of the American Society of Nephrology : JASN · 2016Article
- Deep proteomic profiling of vasopressin-sensitive collecting duct cells. II. Bioinformatic analysis of vasopressin signaling.American journal of physiology. Cell physiology · 2015Article
- Glutathionylation of the aquaporin-2 water channel: a novel post-translational modification modulated by the oxidative stress.The Journal of biological chemistry · 2014Article
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Renal water reabsorption is controlled by arginine vasopressin (AVP), which binds to V2 receptors, resulting in protein kinase A (PKA) activation, phosphorylation of aquaporin 2 (AQP2) at serine 256, and translocation of AQP2 to the plasma membrane. However, AVP also causes dephosphorylation of AQP2 at S261. Recent studies showed that cyclin-dependent kinases (cdks) can phosphorylate AQP2 peptides at S261 in vitro. We investigated the possible role of cdks in the phosphorylation of AQP2 and identified a new PKA-independent pathway regulating AQP2 trafficking. In ex vivo kidney slices and MDCK-AQP2 cells, R-roscovitine, a specific inhibitor of cdks, increased pS256 levels and decreased pS261 levels. The changes in AQP2 phosphorylation status were paralleled by increases in cell surface expression of AQP2 and osmotic water permeability in the absence of forskolin stimulation. R-Roscovitine did not alter cAMP-dependent PKA activity but specifically reduced protein phosphatase 2A (PP2A) expression and activity in MDCK cells. Notably, we found reduced PP2A expression and activity and reduced pS261 levels in Pkd1(+/-) mice displaying a syndrome of inappropriate antidiuresis with high levels of pS256, despite unchanged AVP and cAMP. Similar to previous findings in Pkd1(+/-) mice, R-roscovitine treatment caused a significant decrease in intracellular calcium in MDCK cells. Our data indicate that reduced activity of PP2A, secondary to reduced intracellular Ca(2+) levels, promotes AQP2 trafficking independent of the AVP-PKA axis. This pathway may be relevant for explaining pathologic states characterized by inappropriate AVP secretion and positive water balance.
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