Na,K‐ATPase α1‐subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane

Lecuona, Emilia; Dada, Laura A.; Sun, Haiying; Butti, Maria L.; Zhou, Guofei; Chew, Teng‐Leong; Sznajder, Jacob I.

doi:10.1096/fj.06-6503fje

Cited by 45 publications

(44 citation statements)

References 58 publications

(79 reference statements)

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“…Human lung cancer A549 cells show many characteristics of ATII cells (Lieber et al, 1976), including the regulation of the Na,K-ATPase Lecuona et al, 2006) but do not form tight epithelial monolayers, whereas canine renal epithelial MDCK cells and human gastric epithelial HGE-20 cells form tight junctions. Western blot analysis using two different antibodies against human FXYD5 detected a major band at ∼32 kDa in A549, human ATII (hATII), MDCK and HGE-20 cell lysates (Fig.…”

Section: Resultsmentioning

confidence: 99%

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

Tokhtaeva

Sun

Deiss-Yehiely

et al. 2016

Journal of Cell Science

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FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the transdimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase β 1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the β 1 subunit with intact or mutated β 1 -β 1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the β 1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular β 1 -β 1 interactions, suggesting that the ratio between FXYD5 and α 1 -β 1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.

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Section: Resultsmentioning

confidence: 99%

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

Tokhtaeva

Sun

Deiss-Yehiely

et al. 2016

Journal of Cell Science

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“…A549 cells are from a human alveolar epithelial cell line that shows many characteristics of ATII cells (Lieber et al, 1976), including the regulation of the Na + /K + -ATPase, and are more easily transfected than primary ATII cells Dada et al, 2003;Lecuona et al, 2006). AS160 phosphorylation was assessed with a phospho-Akt substrate (pAS) antibody after immunoprecipitation with a FLAG antibody.…”

Section: -Atpase Translocationmentioning

confidence: 99%

“…A549 cells expressing V5-tagged rat Na + /K + -ATPase  1 subunit were generated as described previously (Lecuona et al, 2006) and grown in DMEM with the addition of 3 M ouabain to suppress the endogenous human Na + /K + -ATPase  1 subunit. Stably transfected GFP-Rab10 A549 cells were generated by transfecting the cells with GFP-WT-Rab10; selection was performed with media containing 1 g/ml puromycin.…”

Section: Isolated Perfused Rat Lung Modelmentioning

confidence: 99%

“…This translocation involves the movement of vesicles containing Na + /K + -ATPase from intracellular pools to the plasma membrane (Ridge et al, 2002). It has been reported that the dephosphorylation of the Na + /K + -ATPase  1 subunit at the serine 18 residue is a major regulator of this process (Lecuona et al, 2006). However, how the signals generated after receptor activation converge to regulate the trafficking steps necessary to translocate vesicles containing Na + /K + -ATPase to the plasma membrane has not yet been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

Comellas

Kelly

Trejo

et al. 2010

Journal of Cell Science

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Stimulation of Na+/K+-ATPase translocation to the cell surface increases active Na+ transport, which is the driving force of alveolar fluid reabsorption, a process necessary to keep the lungs free of edema and to allow normal gas exchange. Here, we provide evidence that insulin increases alveolar fluid reabsorption and Na+/K+-ATPase activity by increasing its translocation to the plasma membrane in alveolar epithelial cells. Insulin-induced Akt activation is necessary and sufficient to promote Na+/K+-ATPase translocation to the plasma membrane. Phosphorylation of AS160 by Akt is also required in this process, whereas inactivation of the Rab GTPase-activating protein domain of AS160 promotes partial Na+/K+-ATPase translocation in the absence of insulin. We found that Rab10 functions as a downstream target of AS160 in insulin-induced Na+/K+-ATPase translocation. Collectively, these results suggest that Akt plays a major role in Na+/K+-ATPase intracellular translocation and thus in alveolar fluid reabsorption.

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“…By contrast, in AECs of normal rats, the stimulation of DA receptors increases lung edema clearance by increasing NKA function. Specific studies have shown that DA promotes protein phosphatase 2A translocation to the membrane fraction, leading to dephosphorylation of the NKAα 1 subunit at the Ser-18 residue and its recruitment to the cell plasma membrane of alveolar epithelial type II (ATII) cells via DA receptors, which results in increased NKA activity (51,52) and lung fluid clearance (53). Moreover, new evidence has revealed that administration of a tyrosine-enriched diet to rats increases endogenous DA production, which causes increased NKA protein abundance in AECs, leading to increased NKA activity via the activation of D 1 receptors (54).…”

Section: Da Receptor-mediated Regulation Of Nkamentioning

confidence: 99%

Crosstalk between dopamine receptors and the Na+/K+-ATPase (Review)

Zhang

Liang³

et al. 2013

Molecular Medicine Reports

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Abstract. Dopamine (DA) receptors, which belong to the G protein-coupled receptor family, are the target of ~50% of all modern medicinal drugs and constitute a large and diverse class of proteins whose primary function is to transduce extracellular stimuli into intracellular signals. Na + /K + -ATPase (NKA) is ubiquitous and crucial for the maintenance of intracellular ion homeostasis and excitability. Furthermore, it plays a critical role in diverse effects, including clinical cardiotonic and cardioprotective effects, ischemic preconditioning in the brain, natriuresis, lung edema clearance and other processes. NKA regulation is of physiological and pharmacological importance and has species-and tissue-specific variations. The activation of DA receptors regulates NKA expression/activity and trafficking in various tissues and cells, for example in the kidney, lung, intestine, brain, non-pigmented ciliary epithelium and the vascular bed. DA receptor-mediated regulation of NKA mediates a diverse range of cellular responses and includes endocytosis/exocytosis, phosphorylation/dephosphorylation of the α subunit of NKA and multiple signaling pathways, including phosphatidylinositol (PI)-phospholipase C/protein kinase (PK) C, cAMP/PKA, PI3K, adaptor protein 2, tyrosine phosphatase and mitogen-activated protein kinase/extracellular signal-regulated protein kinase. Furthermore, in brain and HEK293T cells, D 1 and D 2 receptors exist in a complex with NKA. Among D 1 and D 2 receptors and NKA, regulations are reciprocal, which leads to crosstalk between DA receptors and NKA. In the present study, the current understanding of signaling mechanisms responsible for the crosstalk between DA receptors and NKA, as well as with specific consequent functions, is reviewed.

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Na,K‐ATPase α1‐subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane

Cited by 45 publications

References 58 publications

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell–cell trans-dimerization of Na,K-ATPase β1 subunits

Insulin regulates alveolar epithelial function by inducing Na+/K+-ATPase translocation to the plasma membrane in a process mediated by the action of Akt

Crosstalk between dopamine receptors and the Na+/K+-ATPase (Review)

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