FXYD proteins: new regulators of Na-K-ATPase

Geering, Käthi

doi:10.1152/ajprenal.00126.2005

Cited by 329 publications

(332 citation statements)

References 101 publications

(127 reference statements)

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“…In addition, Fxyd3 (formerly Mat-8) also showed reduced expression. Fxyd3 has been implicated in ion channel regulation, where it may regulate the Na ϩ and K ϩ balance in and around cells (21). There were also large differences in the expression of glycosylation enzymes, suggesting qualitative and quantitative differences in the carbohydrate moieties on glycoproteins and glycolipids (Tables 1 and 2).…”

Section: Altered Cell-cell and Cell-extracellular Matrix (Ecm) Interamentioning

confidence: 99%

Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes

Chaparro¹,

Konigshofer

Beilhack

et al. 2006

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

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Section: Altered Cell-cell and Cell-extracellular Matrix (Ecm) Interamentioning

confidence: 99%

Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes

Chaparro¹,

Konigshofer

Beilhack

et al. 2006

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

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“…However, unlike with SERCA, there is no evidence for phosphorylation of this protein in the resting platelet phosphoproteome [47], although given the need for activation with a strong platelet activator for the Na + /K + -ATPase to be influenced by PKC, phosphorylation of this protein might not be expected under resting conditions. In cardiac muscle and several other cell types, Na + /K + -ATPase activity is modulated by association with members of the FXYD family of proteins [55]. However, no members of the FXYD family have been detected in the platelet proteome [56].…”

Section: Discussionmentioning

confidence: 99%

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

et al. 2015

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Rises in cytosolic Ca 2+ concentration ([Ca 2+ ] cyt ) are central in platelet activation, yet many aspects of the underlying mechanisms are poorly understood. Most studies examine how experimental manipulations affect agonist-evoked rises in [Ca 2+ ] cyt , but these only monitor the net effect of manipulations on the processes controlling [Ca 2+ ] cyt (Ca 2+ buffering, sequestration, release, entry and removal), and cannot resolve the source of the Ca 2+ or the transporters or channels affected. To investigate the effects of protein kinase C (PKC) on platelet Ca 2+ signalling, we here monitor Ca 2+ flux around the platelet by measuring net Ca 2+ fluxes to or from the extracellular space and the intracellular Ca 2+ stores, which act as the major sources and sinks for Ca 2+ influx into and efflux from the cytosol, as well as monitoring the cytosolic Na + concentration ([Na + ] cyt ), which influences platelet Ca 2+ fluxes via Na + /Ca 2+ exchange. The intracellular store Ca 2+ concentration ([Ca 2+ ] st ) was monitored using Fluo-5N, the extracellular Ca 2+ concentration ([Ca 2+ ] ext ) was monitored using Fluo-4 whilst [Ca 2+ ] cyt and [Na + ] cyt were monitored using Fura-2 and SFBI respectively. PKC inhibition using Ro-31-8220 or bisindolaemide I potentiated ADP-and thrombin-evoked rises in [Ca 2+ ] cyt in the absence of extracellular Ca 2+ . PKC inhibition potentiated ADP-evoked but reduced thrombin-evoked intracellular Ca 2+ release and Ca 2+ removal into the extracellular medium. SERCA inhibition using thapsigargin and 2,5-di(tert-butyl) l,4-benzohydroquinone abolished the effect of PKC inhibitors on ADP-evoked changes in [Ca 2+ ] cyt but only reduced the effect on thrombin-evoked responses. Thrombin evokes substantial rises in [Na + ] cyt which would be expected to reduce Ca 2+ removal via the Na + /Ca 2+ exchanger (NCX). Thrombinevoked rises in [Na + ] cyt were potentiated by PKC inhibition, an effect which was not due to altered changes in non-selective cation permeability of the plasma membrane as assessed by Mn 2+ quench of Fura-2 fluorescence. PKC inhibition was without effect on thrombin-evoked rises in [Ca 2+ ] cyt following SERCA inhibition and either removal of extracellular Na + or inhibition of Na + /K + -ATPase activity by removal of extracellular K + or treatment with digoxin. These data suggest that PKC limits ADP-evoked rises in [Ca 2+ ] cyt by acceleration of SERCA activity, whilst rises in [Ca 2+ ] cyt evoked by the stronger platelet activator thrombin are limited by PKC through acceleration of both SERCA and Na + /K + -ATPase activity, with the latter limiting the effect of thrombin on rises in [Na + ] cyt and so forward mode NCX activity. The use of selective PKC inhibitors indicated that conventional and not novel PKC isoforms are responsible for the inhibition of agonist-evoked Ca 2+ signalling.

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“…15,16 Previous studies have shown that the FXYD2 protein is highly enriched in kidney tissue. 17 Furthermore, it is expressed specifically in the distal nephron.…”

mentioning

confidence: 99%

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

et al. 2013

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Chromophobe renal cell carcinoma (RCC) is a form of renal cancer that may be confused with other eosinophilic renal tumors, including oncocytoma, type 2 papillary RCC, and clear-cell RCC with eosinophilic features. There are currently no robust markers to distinguish these neoplasms. Chromophobe RCC and renal oncocytoma are presumably derived from the distal nephron. FXYD2 is a distal tubule regulator of the trimeric Na þ / K þ -transporting ATPase that is enriched in kidney tissue. In this study, we investigated the expression of FXYD2 in normal human kidney, 27 chromophobe RCCs, 30 oncocytomas, 15 clear-cell RCCs, and 11 papillary RCCs. Immunohistochemical staining for FXYD2 showed diffuse, strong immunoreactivity in the basolateral membrane of distal tubules of normal human kidney. Ninety-six percent (26/27) of chromophobe RCCs were immunoreactive for FXYD2 in a distinctly membranous pattern. Twenty-five of these tumors showed at least focal 2 þ staining. In contrast, only 17% (5/30) of renal oncocytomas, 11% (2/15) of clear-cell RCCs, and 0% (0/11) of papillary RCCs displayed FXYD2 immunoreactivity. None of these cases showed Z2 þ FXYD2 staining. A subset of cases was confirmed as oncocytoma or chromophobe RCC using cytokeratin 7, colloidal iron, and interphase fluorescence in situ hybridization analysis of chromosomes 1, 2, 6, 10, and 17. Among this subset, 100% (7/7) of chromophobe RCCs were FXYD2 positive, whereas 17% (2/12) of oncocytomas were stained with FXYD2. The oncocytomas that stained with FXYD2 did so in a weak (1 þ ), patchy manner. In contrast, chromophobe RCCs showed Z2 þ staining in 86% (6/7) of these tumors. For comparison, this subset was also stained for kidney-specific cadherin (Ksp-cadherin). Ksp-cadherin showed positive staining in 100% (7/7) of chromophobe RCCs and 33% (4/12) of oncocytomas. This is the first report demonstrating the potential utility of FXYD2 immunohistochemistry in the diagnosis of chromophobe RCC.

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FXYD proteins: new regulators of Na-K-ATPase

Cited by 329 publications

References 101 publications

Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes

Nonobese diabetic mice express aspects of both type 1 and type 2 diabetes

Conventional protein kinase C isoforms differentially regulate ADP- and thrombin-evoked Ca2+ signalling in human platelets

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

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