Localization of intracellular compartments that exchange Na,K‐ATPase molecules with the plasma membrane in a hormone‐dependent manner

Efendiev, Riad; Das-Panja, K; Cinelli, Angel R.; Bertorello, Alejandro M.; Pedemonte, Carlos H.

doi:10.1038/sj.bjp.0707304

Cited by 23 publications

(20 citation statements)

References 38 publications

(81 reference statements)

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“…These circulating hormones can exert either short term or long term regulation on Na ϩ /K ϩ -ATPase via changing the gene expression level, reversible phosphorylation of its subunits, or modulating its trafficking (14,15). Recently, accumulated evidence indicates that estrogen has a great effect on the activity and expression of Na…”

Section: Namentioning

confidence: 99%

N-myc Downstream-regulated Gene 2, a Novel Estrogen-targeted Gene, Is Involved in the Regulation of Na+/K+-ATPase

Yang²,

Li³

et al. 2011

Journal of Biological Chemistry

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Na؉ /K ؉ -ATPase, a plasma membrane protein abundantly expressed in epithelial tissues, has been identified and linked to numerous biological events, including ion transport and reabsorption. In Na ؉ /K ؉ -ATPase, the ␤-subunit plays a fundamental role in the structural integrity and functional maturation of holoenzyme. Estrogens are important circulating hormones that can regulate Na ؉ /K ؉ -ATPase abundance and activity; however, the specific molecules participating in this process are largely unknown. Here, we characterize that N-myc downstream-regulated gene 2 (NDRG2) is an estrogen up-regulated gene. 17␤-Estradiol binds with estrogen receptor ␤ but not estrogen receptor ␣ to up-regulate NDRG2 expression via transcriptional activation. We also find that NDRG2 interacts with the ␤1-subunit of Na ؉ /K ؉ -ATPase and stabilizes the ␤1-subunit by inhibiting its ubiquitination and degradation. NDRG2-induced prolongation of the ␤1-subunit protein half-life is accompanied by a similar increase in Na ؉ /K ؉ -ATPase-mediated Na ؉ transport and Na ؉ current in epithelial cells. In addition, NDRG2 silencing largely attenuates the accumulation of ␤1-subunit regulated by 17␤-estradiol. Our results demonstrate that estrogen/NDRG2/Na ؉ /K ؉ -ATPase ␤1 pathway is important in promoting Na ؉ /K ؉ -ATPase activity and suggest this novel pathway might have substantial roles in ion transport, fluid balance, and homeostasis. Na ϩ /K ϩ -ATPase, a plasma membrane ion pump, has numerous physiological functions. Of note, it is consisted of three subunits (1), ␣, ␤, and ␥, and the holoenzyme activity required by the participation of the three subunits. ␣ is the catalytic subunit of the enzyme that utilizes ATP hydrolysis to pump K ϩ into the cell in exchange for Na ϩ , which is essential for maintaining normal resting membrane potentials and facilitating the exchange of other materials needed for cellular homeostasis and activity (2-4). ␤-Subunit is responsible for the formation and integrity of the holoenzyme. In vertebrate cells, ␤-subunit may stabilize the correct folding of the ␣-subunit to facilitate its delivery to the plasma membrane (5-7). In addition, evidence showed that ␤-subunit is related to the cell motility and invasion (8, 9). At present, four ␣-isoforms known as ␣1, ␣2, ␣3, ␣4 as well as three different ␤-polypeptides termed as ␤1, ␤2, and ␤3 (3) have been identified. Among these isoforms, ␣1␤1 distributes in nearly every tissue whereas other isoforms exhibit a tissue-specific pattern of expression. ␥-Subunit, a small hydrophobic polypeptide that has only one isoform, is involved in the modulation of Na ϩ /K ϩ -ATPase function (10, 11). The ionic homeostasis maintained by the Na ϩ /K ϩ -ATPase is also critical for cell survival, differentiation, and cell apoptosis (12, 13).As an important molecule in charge of so many biological events, Na ϩ /K ϩ -ATPase is regulated by a number of hormones, including aldosterone, thyroid hormone, glucocorticoid, catecholamines, insulin, carbachol, and androgen. These circulating horm...

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Section: Namentioning

confidence: 99%

N-myc Downstream-regulated Gene 2, a Novel Estrogen-targeted Gene, Is Involved in the Regulation of Na+/K+-ATPase

Yang²,

Li³

et al. 2011

Journal of Biological Chemistry

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“…The second mechanism of regulation is that new Na C /K C -ATPase subunits are delivered to the plasma membrane from intracellular stores when needed (Hundal et al 1992, Al-Khalili et al 2003. It has been shown that Na C /K C -ATPase-containing compartments are located just underneath the plasma membrane (Efendiev et al 2007). Regulation performed through direct effects on the kinetic behavior of the enzyme occurs within minutes to hours and is accomplished through changes in the turnover rate of the existing pumps via the phosphorylation of protein kinase A (PKA), PKC, PKB, or PKG ( Fig.…”

Section: Regulation Of Namentioning

confidence: 99%

“…The isoforms combine to form a number of Na C /K C -ATPase isozymes expressed in a tissue-specific and cell-specific manner (Jorgensen et al 2003). The heterodimeric protein subunits are synthesized independently in the endoplasmic reticulum and assembly during or very soon after synthesis in this organelle (Geering et al 1996, Therien & Blostein 2000, Efendiev et al 2007.…”

Section: Structure and Functionmentioning

confidence: 99%

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

Obradović¹,

Bjelogrlić²,

Rizzo³

et al. 2013

Journal of Endocrinology

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“…In nontreated cells, NKA ␣1 is mostly localized in the plasma membrane region, and AP-1 is in cytosolic regions surrounding the nucleus. We have previously demonstrated that the intracellular compartments containing NKA molecules are close to the plasma membrane and that it is difficult to distinguish between NKA molecules that are at the plasma membrane and in intracellular compartments (38). In cells treated with Ang II, it can be observed that AP-1 molecules have been recruited to the plasma membrane region where the NKA-containing intracellular compartments are located, and consequently the level of FRET N between the fluorophores attached to NKA and AP-1 has been significantly increased (arrows on Fig.…”

Section: Resultsmentioning

confidence: 99%

G-protein-coupled Receptor-mediated Traffic of Na,K-ATPase to the Plasma Membrane Requires the Binding of Adaptor Protein 1 to a Tyr-255-based Sequence in the α-Subunit

Efendiev

Budu

Bertorello

et al. 2008

Journal of Biological Chemistry

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Motion of integral membrane proteins to the plasma membrane in response to G-protein-coupled receptor signals requires selective cargo recognition motifs that bind adaptor protein 1 and clathrin. Angiotensin II, through the activation of AT1 receptors, promotes the recruitment to the plasma membrane of Na,K-ATPase molecules from intracellular compartments. We present evidence to demonstrate that a tyrosinebased sequence (IVVY-255) present within the Na,K-ATPase ␣1-subunit is involved in the binding of adaptor protein 1. Mutation of Tyr-255 to a phenylalanine residue in the Na,KATPase ␣1-subunit greatly reduces the angiotensin II-dependent activation of Na,K-ATPase, recruitment of Na,K-ATPase molecules to the plasma membrane, and association of adaptor protein 1 with Na,K-ATPase ␣1-subunit molecules. To determine protein-protein interaction, we used fluorescence resonance energy transfer between fluorophores attached to the Na,K-ATPase ␣1-subunit and adaptor protein 1. Although angiotensin II activation of AT1 receptors induces a significant increase in the level of fluorescence resonance energy transfer between the two molecules, this effect was blunted in cells expressing the Tyr-255 mutant. Thus, results from different methods and techniques suggest that the Tyr-255-based sequence within the NKA ␣1-subunit is the site of adaptor protein 1 binding in response to the G-protein-coupled receptor signals produced by angiotensin II binding to AT1 receptors.

show abstract

Localization of intracellular compartments that exchange Na,K‐ATPase molecules with the plasma membrane in a hormone‐dependent manner

Cited by 23 publications

References 38 publications

N-myc Downstream-regulated Gene 2, a Novel Estrogen-targeted Gene, Is Involved in the Regulation of Na+/K+-ATPase

N-myc Downstream-regulated Gene 2, a Novel Estrogen-targeted Gene, Is Involved in the Regulation of Na+/K+-ATPase

Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases

G-protein-coupled Receptor-mediated Traffic of Na,K-ATPase to the Plasma Membrane Requires the Binding of Adaptor Protein 1 to a Tyr-255-based Sequence in the α-Subunit

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