Identification of the β-subunit for nongastric H-K-ATPase in rat anterior prostate

Pestov, Nikolay B.; Korneenko, Tatyana V.; Radkov, Rossen; Zhao, Hao; Shakhparonov, M. I.; Modyanov, Nikolaï N.

doi:10.1152/ajpcell.00393.2003

Cited by 28 publications

(20 citation statements)

References 58 publications

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“…No specific b-subunit that assembles with the nongastric H,K-ATPase has been found. Recent studies suggest that the Na,K-ATPase b 1 -subunit is probably the partner for the non-gastric H,K-ATPase isoform in vivo [11].…”

Section: Introductionmentioning

confidence: 99%

“…The gastric H,K-ATPase is located in intracellular tubulovesicular elements in the resting parietal cell and relocates to the secretory canalicular (apical) membrane upon stimulation of acid secretion [17]. The non-gastric H,K-ATPase is found on the apical membranes of epithelial cells in the colon, kidney, and prostate gland [11,[18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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Polarized membrane distribution of potassium-dependent ion pumps in epithelial cells: Different roles of the N-glycans of their β subunits

Vagin

Turdikulova

Tokhtaeva

2007

Cell Biochem Biophys

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The Na,K-ATPases and the H,K-ATPases are two potassium-dependent homologous heterodimeric P2-type pumps that catalyze active transport of Na+ in exchange for K+ (Na,K-ATPase) or H+ in exchange for K+ (H,K-ATPase). The ubiquitous Na,K-ATPase maintains intracellular ion balance and membrane potential. The gastric H,K-ATPase is responsible for acid secretion by the parietal cell of the stomach. Both pumps consist of a catalytic alpha-subunit and a glycosylated beta-subunit that is obligatory for normal pump maturation and trafficking. Individual N-glycans linked to the beta-subunits of the Na,K-ATPase and H,K-ATPase are important for stable membrane integration of their respective alpha subunits, folding, stability, subunit assembly, and enzymatic activity of the pumps. They are also essential for the quality control of unassembled beta-subunits that results in either the exit of the subunits from the ER or their ER retention and subsequent degradation. Overall, the importance of N-glycans for the maturation and quality control of the H,K-ATPase is greater than that of the Na,K-ATPase. The roles of individual N-glycans of the beta-subunits in the post-ER trafficking, membrane targeting and plasma membrane retention of the Na,K-ATPase and H,K-ATPase are different. The Na,K-ATPase beta1-subunit is the major beta-subunit isoform in cells with lateral location of the pump. All three N-glycans of the Na,K-ATPase beta1-subunit are important for the lateral membrane retention of the pump due to glycan-mediated interaction between the beta1-subunits of the two neighboring cells in the cell monolayer and cytosolic linkage of the alpha-subunit to the cytoskeleton. This intercellular beta1-beta1 interaction is also important for formation of cell-cell contacts. In contrast, the N-glycans unique to the Na,K-ATPase beta2-subunit,which has up to eight N-glycosylation sites, contain apical sorting information. This is consistent with the apical location of the Na,K-ATPase in normal and malignant epithelial cells with high abundance of the beta2-subunit. Similarly, all seven N-glycans of the gastric H,K-ATPase beta-subunit determine apical sorting of this subunit.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Polarized membrane distribution of potassium-dependent ion pumps in epithelial cells: Different roles of the N-glycans of their β subunits

Vagin

Turdikulova

Tokhtaeva

2007

Cell Biochem Biophys

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“…Also, nongastric H-K-ATPase does not have a specific ␤-subunit but employs the ␤ 1 isoform of Na-K-ATPase (8,31,42). This fact is relevant to the mechanisms of cellular sorting of X-K-ATPases because H-KATPase and Na-K-ATPase are localized to different membranes in polarized epithelial cells.…”

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confidence: 99%

Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo

Pestov

Korneenko²,

Shakhparonov³

et al. 2006

American Journal of Physiology-Cell Physiology

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The physiological functions of nongastric (colonic) H-K-ATPase (gene symbol Atp12a), unlike those of Na-K-ATPase and gastric H-K-ATPase, are poorly understood. It has been suggested that it pumps Na+ more efficiently than H+; however, so far, there is no direct evidence that it pumps H+ in vivo. Previously, we found that the nongastric H-K-ATPase alpha-subunit is expressed in apical membranes of rodent anterior prostate epithelium, in a complex with the Na-K-ATPase beta1-subunit. Here we report the effects of Atp12a gene ablation on polarization of the beta1-subunit and secretory function of the anterior prostate. In nongastric H-K-ATPase-deficient prostate, the Na-K-ATPase alpha-subunit resided exclusively in basolateral membranes; however, the beta1-subunit disappeared from apical membranes, demonstrating that beta1 is an authentic subunit of nongastric H-K-ATPase in vivo and that apical localization of beta1 in the prostate is completely dependent on its association with the nongastric H-K-ATPase alpha-subunit. A remarkable reduction in acidification of anterior prostate fluids was observed: pH 6.38 +/- 0.14 for wild-type mice and 6.96 +/- 0.10 for homozygous mutants. These results show that nongastric H-K-ATPase is required for acidification of luminal prostate fluids, thereby providing a strong in vivo correlate of previous functional expression studies demonstrating that it operates as a proton pump.

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“…This differential localization and sorting depends on the interaction of ATP12A with the beta-subunit of the Na + /K + ATPase [32]. Recently it has been shown that in the rat anterior prostate the Na + /K + ATPase beta1-subunit functions also as the authentic beta-subunit of the non-gastric H + /K + ATPase and putatively accounts for the intracellular sorting of the X-K-ATPase isoforms [33]. Interestingly, the Na + /K + ATPase beta1-subunit was found to be down-regulated by androgens in human LNCaP-FGC prostate cancer cells and human prostate cancer xenografts [34].…”

Section: Discussionmentioning

confidence: 99%

Expression of the Non-gastric H<sup>+</sup>/K<sup>+</sup> ATPase ATP12A in Normal and Pathological Human Prostate Tissue

Streif

Iglseder

Hauser‐Kronberger

et al. 2011

Cell Physiol Biochem

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Altered cellular proton handling and cell volume regulation are hallmarks of tumorigenesis. To investigate a possible involvement of the non-gastric H⁺/K⁺ ATPase ATP12A (ATP1AL1) in prostate cancer, we performed immunohistochemistry in formalin-fixed, paraffin-embedded histological sections from benign and malignant human prostate lesions. Normal prostate tissue displayed a membrane-bound ATP12A staining with focal accumulated pattern, whereas in the benign prostate hyperplasia (BPH) and cancerous prostate tissue (tumor grade I–III) the protein appears to be displaced in the luminal cells of the glandular epithelium. Hence, the expression pattern of ATP12A is markedly altered in BPH and prostate cancer. To test for altered gene expression of ATP12A we performed quantitative reverse transcriptase PCR (QRT-PCR) in normal (tumor-free) prostate tissue, BPH and tumor stages I–III using a prostate cancer cDNA array. However, no significantly different expression levels could be detected in the various disease states compared to normal tissue, which contrasts the findings from immunohistochemistry and points to the possibility of altered post-translational processing and/or sorting of the protein. We further show that ATP12A mRNA is expressed at different levels in PC-3 and LNCaP prostate cancer cells, with a significant ñ26-fold higher expression in the latter cell type. Protein expression in these tumor cell lines was verified by Western blot.

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Identification of the β-subunit for nongastric H-K-ATPase in rat anterior prostate

Cited by 28 publications

References 58 publications

Polarized membrane distribution of potassium-dependent ion pumps in epithelial cells: Different roles of the N-glycans of their β subunits

Polarized membrane distribution of potassium-dependent ion pumps in epithelial cells: Different roles of the N-glycans of their β subunits

Loss of acidification of anterior prostate fluids in Atp12a-null mutant mice indicates that nongastric H-K-ATPase functions as proton pump in vivo

Expression of the Non-gastric H<sup>+</sup>/K<sup>+</sup> ATPase ATP12A in Normal and Pathological Human Prostate Tissue

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