Ser-261 phospho-regulation is involved in pS256 and pS269-mediated aquaporin-2 apical translocation

Yui, Naofumi; Ando, Fumiaki; Sasaki, Sei; Uchida, Shinichi

doi:10.1016/j.bbrc.2017.06.162

Cited by 12 publications

(8 citation statements)

References 29 publications

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“…In contrast, Lu et al (102) and Moeller et al (113) reported no effect of S261 mutation to a nonphosphorylatable amino acid on AQP2 localization. Yui et al (184) recently reported that S261 phosphorylation is important in AQP2 apical translocation.…”

Section: Ii) S261mentioning

confidence: 99%

From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology

Rinschen

Limbutara

Knepper

et al. 2018

Physiological Reviews

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Classical physiological studies using electrophysiological, biophysical, biochemical, and molecular techniques have created a detailed picture of molecular transport, bioenergetics, contractility and movement, and growth, as well as the regulation of these processes by external stimuli in cells and organisms. Newer systems biology approaches are beginning to provide deeper and broader understanding of these complex biological processes and their dynamic responses to a variety of environmental cues. In the past decade, advances in mass spectrometry-based proteomic technologies have provided invaluable tools to further elucidate these complex cellular processes, thereby confirming, complementing, and advancing common views of physiology. As one notable example, the application of proteomics to study the regulation of kidney function has yielded novel insights into the chemical and physical processes that tightly control body fluids, electrolytes, and metabolites to provide optimal microenvironments for various cellular and organ functions. Here, we systematically review, summarize, and discuss the most significant key findings from functional proteomic studies in renal epithelial physiology. We also identify further improvements in technological and bioinformatics methods that will be essential to advance precision medicine in nephrology.

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Section: Ii) S261mentioning

confidence: 99%

From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology

Rinschen

Limbutara

Knepper

et al. 2018

Physiological Reviews

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“…The specific membrane polarities of these molecules can modify and fine-tune the dynamics of actin polymerization. The differences in actin-organizing mechanisms between apical and basolateral sides of kidney epithelial cells may explain why plasma membrane accumulation of AQP2 is prolonged only in the apical plasma membranes after vasopressin treatment, while increased basolateral accumulation is associated with other conditions and treatments both in vivo and in vitro [24,26,30,65,66].…”

Section: Discussionmentioning

confidence: 99%

Chlorpromazine Induces Basolateral Aquaporin-2 Accumulation via F-Actin Depolymerization and Blockade of Endocytosis in Renal Epithelial Cells

Bouley

Yui

Terlouw

et al. 2020

Cells

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We previously showed that in polarized Madin-Darby canine kidney (MDCK) cells, aquaporin-2 (AQP2) is continuously targeted to the basolateral plasma membrane from which it is rapidly retrieved by clathrin-mediated endocytosis. It then undertakes microtubule-dependent transcytosis toward the apical plasma membrane. In this study, we found that treatment with chlorpromazine (CPZ, an inhibitor of clathrin-mediated endocytosis) results in AQP2 accumulation in the basolateral, but not the apical plasma membrane of epithelial cells. In MDCK cells, both AQP2 and clathrin were concentrated in the basolateral plasma membrane after CPZ treatment (100 µM for 15 min), and endocytosis was reduced. Then, using rhodamine phalloidin staining, we found that basolateral, but not apical, F-actin was selectively reduced by CPZ treatment. After incubation of rat kidney slices in situ with CPZ (200 µM for 15 min), basolateral AQP2 and clathrin were increased in principal cells, which simultaneously showed a significant decrease of basolateral compared to apical F-actin staining. These results indicate that clathrin-dependent transcytosis of AQP2 is an essential part of its trafficking pathway in renal epithelial cells and that this process can be inhibited by selectively depolymerizing the basolateral actin pool using CPZ.Cells 2020, 9, 1057 2 of 18 mechanisms of water channel accumulation in the apical plasma membrane of collecting duct cells have been of particular interest, the regulation of basolateral AQP2 has also been investigated in several studies [22][23][24][25][26]. In the cortical connecting segment, basolateral AQP2 is usually readily detectable [23], and AQP2 has varying levels of basolateral expression in collecting duct principal cells from kidney cortex to medulla, with the most obvious basolateral expression in the inner medulla. In MDCK cells, derived from canine kidney, transfected AQP2 usually accumulates in the apical membrane upon intracellular cAMP elevation. However, AQP2 instead concentrates on the basolateral membrane after forskolin (FK) treatment under hypertonic conditions [26]. Importantly, Sec6, Sec8, and RalA, all components of the exocyst, which targets proteins to the basolateral plasma membrane [27], were associated with AQP2-containing vesicles upon mass spectrometry analysis [28]. Furthermore, we showed that AQP2 is necessary for cell migration and tubule morphogenesis through its RGD-regulated interaction with basolateral integrin-β1 [29]. These previous findings all pointed to the existence of an AQP2 basolateral targeting pathway, and indeed we demonstrated the existence of a transcytotic pathway for AQP2 in MDCK cells by blocking basolateral AQP2 during its transit through this membrane domain using low temperature [30]. After initial basolateral targeting, AQP2 is retrieved into Rab5-positive vesicles, then undertakes microtubule-dependent transcytosis to apical recycling vesicles [30]. This novel trafficking concept is supported by an apical plasma membrane proteomics study using mpkCCD cel...

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“…On the other hand, vasopressin increases AQP2 phosphorylation at S269 and decreases AQP2 phosphorylation at S261. These changes in AQP2 phosphorylation status at S261 and S269 have been well-correlated to translocation of AQP2 to the apical plasma membrane 9 , 10 .…”

Section: Introductionmentioning

confidence: 87%

AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

et al. 2018

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Congenital nephrogenic diabetes insipidus (NDI) is characterized by the inability of the kidney to concentrate urine. Congenital NDI is mainly caused by loss-of-function mutations in the vasopressin type 2 receptor (V2R), leading to impaired aquaporin-2 (AQP2) water channel activity. So far, treatment options of congenital NDI either by rescuing mutant V2R with chemical chaperones or by elevating cyclic adenosine monophosphate (cAMP) levels have failed to yield effective therapies. Here we show that inhibition of A-kinase anchoring proteins (AKAPs) binding to PKA increases PKA activity and activates AQP2 channels in cortical collecting duct cells. In vivo, the low molecular weight compound 3,3′-diamino-4,4′-dihydroxydiphenylmethane (FMP-API-1) and its derivatives increase AQP2 activity to the same extent as vasopressin, and increase urine osmolality in the context of V2R inhibition. We therefore suggest that FMP-API-1 may constitute a promising lead compound for the treatment of congenital NDI caused by V2R mutations.

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Ser-261 phospho-regulation is involved in pS256 and pS269-mediated aquaporin-2 apical translocation

Cited by 12 publications

References 29 publications

From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology

From Molecules to Mechanisms: Functional Proteomics and Its Application to Renal Tubule Physiology

Chlorpromazine Induces Basolateral Aquaporin-2 Accumulation via F-Actin Depolymerization and Blockade of Endocytosis in Renal Epithelial Cells

AKAPs-PKA disruptors increase AQP2 activity independently of vasopressin in a model of nephrogenic diabetes insipidus

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