Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells

Bouley, Richard; Breton, Sylvie; Sun, Tiffany; McLaughlin, Margaret; Nsumu, Ndona N.; Lin, Herbert Y.; Ausiello, Dennis A.; Brown, Dennis

doi:10.1172/jci9594

Cited by 210 publications

(247 citation statements)

References 54 publications

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“…Surprisingly, this targeting occurred without significant changes in intracellular cAMP. It has previously been demonstrated that AQP2 can traffic in renal epithelial cells without alterations in cAMP levels, such as following hypertonic challenge (21) or stimulation of the cGMP pathway via nitric oxide (22). The fact that our EP4 selective agonist seemingly acts upon its G-protein-coupled receptor without a significant rise in intracellular cAMP could indicate that the receptor is acting on AQP2 through another pathway, possibly an effect of β-arrestindependent signaling (23,24).…”

Section: Acute Pge2 and Butaprost Treatment Increases Aqp2 Membranementioning

confidence: 81%

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus

Olesen

Rützler

Moeller

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

113

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In the kidney, the actions of vasopressin on its type-2 receptor (V2R) induce increased water reabsorption alongside polyphosphorylation and membrane targeting of the water channel aquaporin-2 (AQP2). Loss-of-function mutations in the V2R cause Xlinked nephrogenic diabetes insipidus. Treatment of this condition would require bypassing the V2R to increase AQP2 membrane targeting, but currently no specific pharmacological therapy is available. The present study examined specific E-prostanoid receptors for this purpose. In vitro, prostaglandin E2 (PGE2) and selective agonists for the E-prostanoid receptors EP2 (butaprost) or EP4 (CAY10580) all increased trafficking and ser-264 phosphorylation of AQP2 in Madin-Darby canine kidney cells. Only PGE2 and butaprost increased cAMP and ser-269 phosphorylation of AQP2. Ex vivo, PGE2, butaprost, or CAY10580 increased AQP2 phosphorylation in isolated cortical tubules, whereas PGE2 and butaprost selectively increased AQP2 membrane accumulation in kidney slices. In vivo, a V2R antagonist caused a severe urinary concentrating defect in rats, which was greatly alleviated by treatment with butaprost. In conclusion, EP2 and EP4 agonists increase AQP2 phosphorylation and trafficking, likely through different signaling pathways. Furthermore, EP2 selective agonists can partially compensate for a nonfunctional V2R, providing a rationale for new treatment strategies for hereditary nephrogenic diabetes insipidus.T he anti-diuretic hormone vasopressin (VP) controls wholebody water balance mainly by regulating the water permeability of the kidney collecting duct. VP binds to the Gs-proteincoupled VP type 2 receptor (V2R) in collecting duct principal cells, stimulating the accumulation of aquaporin-2 (AQP2) in the apical plasma membrane (1). This process increases the water permeability of the epithelium, allowing water to be reabsorbed from the collecting-duct lumen and increasing the concentration of the urine. The intracellular signaling cascades of VP in the collecting duct involve increased cAMP and protein kinasedependent phosphorylation of AQP2 at ser-256, ser-264, and ser-269. The ser-256 and ser-269 sites appear to be essential for apical membrane accumulation of AQP2 (2). Although VP's role is well characterized, there is evidence that alternative mechanisms may also regulate water permeability. For example, functional studies on collecting ducts have shown an EC 50 of 10 −11 M for VP-induced increases in water permeability and a requirement of 10 −8 M for maximal effect (3). Water restriction does not increase plasma VP to these levels (4-6). This leaves room for additional mechanisms to be involved in modulating collecting-duct water permeability, supported by evidence that the urinary concentrating ability of the kidney can increase in the presence of a V2R antagonist during water restriction (7).Prostanoids are a family of arachidonic acid derivatives produced in most cell types. The biological actions of one class of prostanoids, prostaglandin E2 (PGE2), are diverse. This may...

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Section: Acute Pge2 and Butaprost Treatment Increases Aqp2 Membranementioning

confidence: 81%

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus

Olesen

Rützler

Moeller

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

113

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“…Control and metabolic acidosis together with dehydration, showed the subapical localization of AQP2 mainly in the collecting ducts ( Figure 6). Bouley et al 26 clearly showed the vasopressin-induced translocation of AQP2 to the apical plasma membrane in the collecting duct principal cells. As our control rats showed high urine osmolality (1670 mOsm per kg H 2 O), AQP2 was thought to be present mainly in the apical plasma membrane even in the control condition.…”

Section: Discussionmentioning

confidence: 99%

Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts

et al. 2009

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Renal aquaporin-2 (AQP2) expression plays a key role in urine concentration. However, it is not known whether metabolic acidosis affects urine-concentrating ability through AQP2 expression in the kidney and urine. We examined urinary excretion and renal expression of AQP2 in control and acidosis rats, using RT-competitive PCR, immunoblot and immunocytochemistry. Urinary excretion of AQP2 is decreased by 92% even with the increase in AQP2 mRNA and protein expressions in the collecting ducts by metabolic acidosis in rats. Urine osmolality in control rats was 1670 ± 198 mOsm per kg H 2 O, and immunocytochemistry revealed the presence of AQP2 in the apical plasma membrane of the principal cells in the collecting ducts. Urine osmolality in acidosis rats was lower than that in control (1397±243 mOsm per kg H 2 O), and immunocytochemistry showed the diffuse presence of AQP2 in the cytoplasm of the principal cells. Differential centrifugationcoupled immunoblot showed a significant decrease in the ratio of AQP2 in plasma membrane-enriched fraction to that in intracellular vesicle-enriched fraction by metabolic acidosis. In summary, AQP2 translocation is largely decreased by metabolic acidosis even with increased expression in the collecting ducts. A disorder of AQP2 translocation in the collecting ducts with acidosis may be responsible for the diuresis in patients with chronic renal failure.

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“…This bait protein was engineered as a single fusion peptide consisting of GAL4:DBD, plus the sequence coding for amino acids Met 1 -Glu 16 from the N terminus of AQP2, Ala 147 -Ala 161 from the second intracellular loop of AQP2, and Asn 220 -Ala 271 from the C-tail of AQP2. The coding sequence of this C-terminal chimera construct was also subcloned into the bacterial expression vector pET41a (Novagen) as a fusion protein with a GST tag on its N terminus (39). All the constructs were sequenced to confirm their reading frame and predicted composition.…”

Section: Methodsmentioning

confidence: 99%

Heat Shock Protein 70 Interacts with Aquaporin-2 and Regulates Its Trafficking

Sun²,

Matsuzaki

et al. 2007

Journal of Biological Chemistry

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113

115

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The trafficking of aquaporin-2 (AQP2) involves multiple complex pathways, including regulated, cAMP-, and cGMP-mediated pathways, as well as a constitutive recycling pathway. Although several accessory proteins have been indirectly implicated in AQP2 recycling, the direct protein-protein interactions that regulate this process remain largely unknown. Using yeast two-hybrid screening of a human kidney cDNA library, we have identified the 70-kDa heat shock proteins as AQP2-interacting proteins. Interaction was confirmed by mass spectrometry of proteins pulled down from rat kidney papilla extract using a GST-AQP2 C-terminal fusion protein (GST-A2C) as a bait, by co-immunoprecipitation (IP) assays, and by direct binding assays using purified hsc70 and the GST-A2C. The direct interaction of AQP2 with hsc70 is partially inhibited by ATP, and the Ser-256 residue in the AQP2 C terminus is important for this direct interaction. Vasopressin stimulation in cells enhances the interaction of hsc70 with AQP2 in IP assays, and vasopressin stimulation in vivo induces an increased co-localization of hsc70 and AQP2 on the apical membrane of principal cells in rat kidney collecting ducts. Functional knockdown of hsc70 activity in AQP2 expressing cells results in membrane accumulation of AQP2 and reduced endocytosis of rhodaminetransferrin. Our data also show that AQP2 interacts with hsp70 in multiple in vitro binding assays. Finally, in addition to hsc70 and hsp70, AQP2 interacts with several other key components of the endocytotic machinery in co-IP assays, including clathrin, dynamin, and AP2. To summarize, we have identified the 70-kDa heat shock proteins as a AQP2 interactors and have shown for hsc70 that this interaction is involved in AQP2 trafficking.Aquaporin 2 is expressed in principal cells of the kidney collecting duct and mediates water absorption and urinary concentration in response to vasopressin (VP). 4 Upon stimulation by VP, AQP2 accumulates on the plasma membrane of collecting duct principal cells (1-4). Activation of both cAMP-dependent, VP/forskolin-stimulated and cAMP-independent, cGMP-responsive signaling pathways stimulates membrane accumulation of AQP2 (5). Recent evidence also indicates that cAMP-and cGMP-independent membrane accumulation of AQP2 can also occur in the absence of hormonal stimulation (6 -8), such as by blocking endocytosis (6, 8) and by disrupting the actin cytoskeleton (9, 10).Although the complicated pathways of intracellular AQP2 trafficking remain to be completely elucidated, even less is known about the direct interaction of AQP2 or AQP2-containing vesicles with a host of accessory factors that must be involved in these processes. Understanding these interactions is a critical step in dissecting the processes of exocytosis, endocytosis, intracellular translocation, as well as degradation and shedding of AQP2 that all contribute to the final physiological response to VP in vivo. Many of the cytosolic proteins known to be involved in vesicular trafficking in general have also been impli...

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Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells

Cited by 210 publications

References 54 publications

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus

Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus

Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts

Heat Shock Protein 70 Interacts with Aquaporin-2 and Regulates Its Trafficking

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