Seminars in Nephrology
Volume 25, Issue 5 , Pages 304-311 , September 2005

FXYD Proteins: Tissue-Specific Regulators of the Na,K-ATPase

  • Haim Garty

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Haim Garty, PhD, Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
    • ,
  • Steven J.D. Karlish

References 

  1. Feraille E , Doucet A . Sodium-potassium-adenosine triphosphatase-dependent sodium transport in the kidney (Hormonal control) . Physiol Rev . 2001;81:345–418
  2. Blanco G , Mercer RW . Isozymes of the Na-K-ATPase (Heterogeneity in structure, diversity in function) . Am J Physiol . 1998;275:F633–F650
  3. Schoner W . Endogenous cardiac glycosides, a new class of steroid hormones . Eur J Biochem . 2002;269:2440–2448
  4. Blaustein MP . Endogenous ouabain (Role in the pathogenesis of hypertension) . Kidney Int . 1996;49:1748–1753
  5. Xie Z , Askari A . Na(+)/K(+)-ATPase as a signal transducer . Eur J Biochem . 2002;269:2434–2439
  6. Sweadner KJ , Rael E . The FXYD gene family of small ion transport regulators or channels (cDNA sequence, protein signature sequence, and expression) . Genomics . 2000;68:41–56
  7. Cornelius F , Mahmmoud YA . Functional modulation of the sodium pump (The regulatory proteins “Fixit”) . News Physiol Sci . 2003;18:119–124
  8. Crambert G , Geering K . FXYD proteins (New tissue-specific regulators of the ubiquitous Na,K-ATPase) . Sci STKE . 2003;166:RE1
  9. Crambert G , Fuzesi M , Garty H , et al.   Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties . Proc Natl Acad Sci U S A . 2002;99:11476–11481
  10. Beguin P , Wang X , Firsov D , et al.   The gamma subunit is a specific component of the Na,K-ATPase and modulates its transport function . EMBO J . 1997;16:4250–4260
  11. Pu HX , Cluzeaud F , Goldshleger R , et al.   Functional role and immunocytochemical localization of the gamma a and gamma b forms of the Na,K-ATPase gamma subunit . J Biol Chem . 2001;276:20370–20378
  12. Garty H , Lindzen M , Scanzano R , et al.   A functional interaction between CHIF and Na-K-ATPase (Implication for regulation by FXYD proteins) . Am J Physiol . 2002;283:F607–F615
  13. Beguin P , Crambert G , Guennoun S , et al.   CHIF, a member of the FXYD protein family, is a regulator of Na,K-ATPase distinct from the gamma-subunit . EMBO J . 2001;20:3993–4002
  14. Beguin P , Crambert G , Monnet-Tschudi F , et al.   FXYD7 is a brain-specific regulator of Na,K-ATPase alpha 1-beta isozymes . EMBO J . 2002;21:3264–3273
  15. Walaas SI , Czernik AJ , Olstad OK , et al.   Protein kinase C and cyclic AMP-dependent protein kinase phosphorylate phospholemman, an insulin and adrenaline-regulated membrane phosphoprotein, at specific sites in the carboxy terminal domain . Biochem J . 1994;304:635–640
  16. Fuller W , Eaton P , Bell JR , et al.   Ischemia-induced phosphorylation of phospholemman directly activates rat cardiac Na/K-ATPase . FASEB J . 2004;18:197–199
  17. Mahmmoud YA , Cramb G , Maunsbach AB , et al.   Regulation of Na,K-ATPase by PLMS, the phospholemman-like protein from shark (Molecular cloning, sequence, expression, cellular distribution, and functional effects of PLMS) . J Biol Chem . 2003;278:37427–37438
  18. Therien AG , Goldshleger R , Karlish SJ , et al.   Tissue-specific distribution and modulatory role of the gamma subunit of the Na,K-ATPase . J Biol Chem . 1997;272:32628–32634
  19. Shi H , Levy-Holzman R , Cluzeaud F , et al.   Membrane topology and immunolocalization of CHIF in kidney and intestine . Am J Physiol . 2001;280:F505–F512
  20. Sweadner KJ , Arystarkhova E , Donnet C , et al.   FXYD proteins as regulators of the Na,K-ATPase in the kidney . Ann N Y Acad Sci . 2003;986:382–387
  21. Jones DH , Golding MC , Barr KJ , et al.   The mouse Na+-K+-ATPase gamma-subunit gene (Fxyd2) encodes three developmentally regulated transcripts . Physiol Genomics . 2001;6:129–135
  22. Bogaev RC , Jia LG , Kobayashi YM , et al.   Gene structure and expression of phospholemman in mouse . Gene . 2001;271:69–79
  23. Kuster B , Shainskaya A , Pu HX , et al.   A new variant of the gamma subunit of renal Na,K-ATPase. Identification by mass spectrometry, antibody binding, and expression in cultured cells . J Biol Chem . 2000;275:18441–18446
  24. Arystarkhova E , Donnet C , Asinovski NK , et al.   Differential regulation of renal Na,K-ATPase by splice variants of the gamma subunit . J Biol Chem . 2002;277:10162–10172
  25. Wetzel RK , Sweadner KJ . Phospholemman expression in extraglomerular mesangium and afferent arteriole of the juxtaglomerular apparatus . Am J Physiol . 2003;285:F121–F129
  26. Pihakaski-Maunsbach K , Vorum H , Locke EM , et al.   Immunocytochemical localization of Na,K-ATPase gamma subunit and CHIF in inner medulla of rat kidney . Ann N Y Acad Sci . 2003;986:401–409
  27. Farman N , Fay M , Cluzeaud F . Cell-specific expression of three members of the FXYD family along the renal tubule . Ann N Y Acad Sci . 2003;986:428–436
  28. Arystarkhova E , Wetzel RK , Sweadner KJ . Distribution and oligomeric association of splice forms of Na(+)-K(+)-ATPase regulatory gamma-subunit in rat kidney . Am J Physiol . 2002;282:F393–F407
  29. Wetzel RK , Sweadner KJ . Immunocytochemical localization of Na-K-ATPase alpha- and gamma-subunits in rat kidney . Am J Physiol . 2001;281:F531–F545
  30. Feschenko MS , Donnet C , Wetzel RK , et al.   Phospholemman, a single-span membrane protein, is an accessory protein of Na,K-ATPase in cerebellum and choroid plexus . J Neurosci . 2003;23:2161–2169
  31. Mercer RW , Biemesderfer D , Bliss DP , et al.   Molecular cloning and immunological characterization of the gamma polypeptide, a small protein associated with the Na,K-ATPase . J Cell Biol . 1993;121:579–586
  32. Therien AG , Karlish SJ , Blostein R . Expression and functional role of the gamma subunit of the Na, K-ATPase in mammalian cells . J Biol Chem . 1999;274:12252–12256
  33. Arystarkhova E , Wetzel RK , Asinovski NK , et al.   The gamma subunit modulates Na(+) and K(+) affinity of the renal Na,K-ATPase . J Biol Chem . 1999;274:33183–33185
  34. Zouzoulas A , Therien AG , Scanzano R , et al.   Modulation of Na,K-ATPase by the gamma subunit (Studies with transfected cells and transmembrane mimetic peptides) . J Biol Chem . 2003;278:40437–40441
  35. Forbush B , Kaplan JH , Hoffman JF . Characterization of a new photoaffinity derivative of ouabain (Labeling of the large polypeptide and of a proteolipid component of the Na, K-ATPase) . Biochemistry . 1978;17:3667–3676
  36. Mahmmoud YA , Vorum H , Cornelius F . Identification of a phospholemman-like protein from shark rectal glands . Evidence for indirect regulation of Na,K-ATPase by protein kinase c via a novel member of the FXYDY family. J Biol Chem . 2000;275:35969–35977
  37. Crambert G , Beguin P , Uldry M , et al.   FXYD7, the first brain- and isoform-specific regulator of Na,K-ATPase (Biosynthesis and function of its posttranslational modifications) . Ann N Y Acad Sci . 2003;986:444–448
  38. Barlet-Bas C , Cheval L , Khadouri C , et al.   Difference in the Na affinity of Na(+)-K(+)-ATPase along the rabbit nephron (Modulation by K) . Am J Physiol . 1990;259:F246–F250
  39. Aizman R , Asher C , Fuzesi M , et al.   Generation and phenotypic analysis of CHIF knockout mice . Am J Physiol . 2002;283:F569–F577
  40. Goldschimdt I , Grahammer F , Warth R , et al.   Kidney and colon electrolyte transport in CHIF knockout mice . Cell Physiol Biochem . 2004;14:113–120
  41. Meij IC , Koenderink JB , van Bokhoven H , et al.   Dominant isolated renal magnesium loss is caused by misrouting of the Na(+),K(+)-ATPase gamma-subunit . Nat Genet . 2000;26:265–266
  42. Dai LJ , Ritchie G , Kerstan D , et al.   Magnesium transport in the renal distal convoluted tubule . Physiol Rev . 2001;81:51–84
  43. Pu HX , Scanzano R , Blostein R . Distinct regulatory effects of the Na,K-ATPase gamma subunit . J Biol Chem . 2002;277:20270–20276
  44. Capasso JM , Rivard CJ , Berl T . Long-term adaptation of renal cells to hypertonicity (Role of MAP kinases and Na-K-ATPase) . Am J Physiol . 2001;280:F768–F776
  45. Capasso JM , Rivard C , Berl T . The expression of the gamma subunit of Na-K-ATPase is regulated by osmolality via C-terminal Jun kinase and phosphatidylinositol 3-kinase-dependent mechanisms . Proc Natl Acad Sci U S A . 2001;98:13414–13419
  46. Capasso JM , Rivard CJ , Enomoto LM , et al.   Chloride, not sodium, stimulates expression of the gamma subunit of Na/K-ATPase and activates JNK in response to hypertonicity in mouse IMCD3 cells . Proc Natl Acad Sci U S A . 2003;100:6428–6433
  47. Jones DH , Davies TC , Kidder GM . Embryonic expression of the putative gamma subunit of the sodium pump is required for acquisition of fluid transport capacity during mouse blastocyst development . J Cell Biol . 1997;139:1545–1552
  48. Lindzen M , Aizman R , Lifshitz Y , et al.   Structure-function relations of interactions between Na,K-ATPase, the gamma subunit, and corticosteroid hormone-induced factor . J Biol Chem . 2003;278:18738–18743
  49. Therien AG , Deber CM . Oligomerization of a peptide derived from the transmembrane region of the sodium pump gamma subunit (Effect of the pathological mutation G41R) . J Mol Biol . 2002;322:583–590
  50. Russ WP , Engelman DM . The GxxxG motif (A framework for transmembrane helix-helix association) . J Mol Biol . 2000;296:911–919
  51. Hebert H , Purhonen P , Vorum H , et al.   Three-dimensional structure of renal Na,K-ATPase from cryo-electron microscopy of two-dimensional crystals . J Mol Biol . 2001;314:479–494
  52. Toyoshima C , Asahi M , Sugita Y , et al.   Modeling of the inhibitory interaction of phospholamban with the Ca2+ ATPase . Proc Natl Acad Sci U S A . 2003;100:467–472
  53. Donnet C , Arystarkhova E , Sweadner KJ . Thermal denaturation of the Na,K-ATPase provides evidence for alpha-alpha oligomeric interaction and gamma subunit association with the C-terminal domain . J Biol Chem . 2001;276:7357–7365
  54. Li C , Grosdidier A , Crambert G , et al.   Structural and functional interaction sites between Na,K-ATPase and FXYD proteins . J Biol Chem . 2004;279:38895–38902
  55. Fuzesi M , Goldshleger R , Garty H , et al.   Defining the nature and sites of interaction between FXYD proteins and Na,K-ATPase . Ann N Y Acad Sci . 2003;986:532–533
  56. Marassi FM , Crowell KJ . Hydration-optimized oriented phospholipid bilayer samples for solid-state NMR structural studies of membrane proteins . J Magn Reson . 2003;161:64–69
  57. Palmer CJ , Scott BT , Jones LR . Purification and complete sequence determination of the major plasma membrane substrate for cAMP-dependent protein kinase and protein kinase C in myocardium . J Biol Chem . 1991;266:11126–11130
  58. Moorman JR , Palmer CJ , John JE , et al.   Phospholemman expression induces a hyperpolarization-activated chloride current in Xenopus oocytes . J Biol Chem . 1992;267: 14551–11454
  59. Moorman JR , Jones LR . Phospholemman (A cardiac taurine channel involved in regulation of cell volume) . Adv Exp Med Biol . 1998;442:3219–3228
  60. Morrison BW , Leder P . Neu and ras initiate murine mammary tumors that share genetic markers generally absent in c-myc and int-2-initiated tumors . Oncogene . 1994;9:3417–3426
  61. Morrison BW , Moorman JR , Kowdley GC , et al.   Mat-8, a novel phospholemman-like protein expressed in human breast tumors, induces a chloride conductance in Xenopus oocytes . J Biol Chem . 1995;270:2176–2182
  62. Attali B , Latter H , Rachamim N , et al.   A corticosteroid-induced gene expressing an “IsK-like” K+ channel activity in Xenopus oocytes . Proc Natl Acad Sci U S A . 1995;92:6092–6096
  63. Minor NT , Sha Q , Nichols CG , et al.   The gamma subunit of the Na,K-ATPase induces cation channel activity . Proc Natl Acad Sci U S A . 1998;95:6521–6525
  64. Sha Q , Lansbery KL , Distefano D , et al.   Heterologous expression of the Na(+),K(+)-ATPase gamma subunit in Xenopus oocytes induces an endogenous, voltage-gated large diameter pore . J Physiol . 2001;535:407–417
  65. Jespersen T , Grunnet M , Rasmussen HB , et al.   The corticosteroid hormone induced factor (CHIF) (A new modulator of KCNQ1 channels?) . Biophys J . 2003;84:16a
  66. Fu X , Kamps MP . E2a-Pbx1 induces aberrant expression of tissue-specific and developmentally regulated genes when expressed in NIH 3T3 fibroblasts . Mol Cell Biol . 1997;17:1503–1512
  67. Ino Y , Gotoh M , Sakamoto M , et al.   Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis . Proc Natl Acad Sci U S A . 2002;99:365–370
  68. Mirza MA , Zhang XQ , Ahlers BA , et al.   Effects of phospholemman downregulation on contractility and [Ca(2+)]i transients in adult rat cardiac myocytes . Am J Physiol . 2004;286:H1322–H1330
  69. Song J , Zhang XQ , Carl LL , et al.   Overexpression of phospholemman alters contractility and [Ca(2+)](i) transients in adult rat myocytes . Am J Physiol . 2002;283:H576–H583
  70. Zhang XQ , Qureshi A , Song J , et al.   Phospholemman modulates Na+/Ca2+ exchange in adult rat cardiac myocytes . Am J Physiol . 2003;284:H225–H233
  71. Ferrandi M , Molinari I , Barassi P , et al.   Organ hypertrophic signaling within caveolae membrane subdomains triggered by ouabain and antagonized by PST 2238 . J Biol Chem . 2004;279:33306–33314
  72. Liu L , Mohammadi K , Aynafshar B , et al.   Role of caveolae in signal-transducing function of cardiac Na+/K+-ATPase . Am J Physiol . 2003;284:C1550–C1560
  73. Garty H , Lindzen M , Fuzesi M , et al.   A specific functional interaction between CHIF and Na,K-ATPase (Role of FXYD proteins in the cellular regulation of the pump) . Ann N Y Acad Sci . 2003;986:395–400

 Supported by research grants from the Israel Science Foundation and the Minerva Foundation. Incumbents of the Hella and Derrick Kleeman (H.G.) and William Smithburg (S.K.) professorial chairs of Biochemistry.

PII: S0270-9295(05)00048-3

doi: 10.1016/j.semnephrol.2005.03.005

Seminars in Nephrology
Volume 25, Issue 5 , Pages 304-311 , September 2005

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