Journal of Bioenergetics and Biomembranes

, Volume 37, Issue 6, pp 387–392 | Cite as

Function of FXYD Proteins, Regulators of Na, K-ATPase

  • Käthi Geering


In this short review, we summarize our work on the role of members of the FXYD protein family as tissue-specific modulators of Na, K-ATPase. FXYD1 or phospholemman, mainly expressed in heart and skeletal muscle increases the apparent affinity for intracellular Na+ of Na, K-ATPase and may thus be important for appropriate muscle contractility. FXYD2 or γ subunit and FXYD4 or CHIF modulate the apparent affinity for Na+ of Na, K-ATPase in an opposite way, adapted to the physiological needs of Na+ reabsorption in different segments of the renal tubule. FXYD3 expressed in stomach, colon, and numerous tumors also modulates the transport properties of Na, K-ATPase but it has a lower specificity of association than other FXYD proteins and an unusual membrane topology. Finally, FXYD7 is exclusively expressed in the brain and decreases the apparent affinity for extracellular K+, which may be essential for proper neuronal excitability.

Key Words

FXYD proteins Na, K-ATPase regulation Na+ reabsorption muscle contractility neuronal excitability 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arystarkhova, E., Wetzel, R. K., Asinovski, N. K., and Sweadner, K. J. (1999). J. Biol. Chem. 274, 33183–33185.CrossRefGoogle Scholar
  2. Attali, B., Latter, H., Rachamim, N., and Garty, H. (1995). Proc. Natl. Acad. Sci. U.S.A. 92, 6092–6096.Google Scholar
  3. Béguin, P., Crambert, G., Guennoun, S., Garty, H., Horisberger, J.-D., and Geering, K. (2001). EMBO J. 20, 3993–4002.CrossRefGoogle Scholar
  4. Béguin, P., Crambert, G., Monnet-Tschudi, F., Uldry, M., Horisberger, J.-D., Garty, H., and Geering, K. (2002). EMBO J. 21, 3264–3273.CrossRefGoogle Scholar
  5. Béguin, P., Wang, X. Y., Firsov, D., Puoti, A., Claeys, D., Horisberger, J. D., and Geering, K. (1997). EMBO J. 16, 4250–4260.CrossRefGoogle Scholar
  6. Chen, L.-S.K., Lo, C. F., Numann, R., and Cuddy, M. (1997). Genomics 41, 435–443.CrossRefGoogle Scholar
  7. Crambert, G., Fuzesi, M., Garty, H., Karlish, S., and Geering, K. (2002). Proc. Natl. Acad. Sci. U.S.A. 99, 11476–11481.CrossRefGoogle Scholar
  8. Crambert, G., and Geering, K. (2003). Sci. STKE 166, RE1.Google Scholar
  9. Crambert, G., Hasler, U., Beggah, A. T., Yu, C., Modyanov, N. N., Horisberger, J. D., Lelievre, L., and Geering, K. (2000). J. Biol. Chem. 275, 1976–1986.CrossRefGoogle Scholar
  10. Crambert, G., Li, C., Claeys, D., and Geering, K. (2005). Mol. Biol. Cell 16, 2363–2371.CrossRefGoogle Scholar
  11. Crambert, G., Li, C., Swee, L. K., and Geering, K. (2004). J. Biol. Chem. 279, 30888–30895.CrossRefGoogle Scholar
  12. Feraille, E., and Doucet, A. (2001). Physiol. Rev. 81, 345–418.Google Scholar
  13. Forbush, B. III, Kaplan, J. H., and Hoffman, J. F. (1978). Biochemistry 17, 3667–3676.CrossRefGoogle Scholar
  14. Fu, X., and Kamps, M. (1997). Mol. Cell. Biol. 17, 1503–1512.Google Scholar
  15. Garty, H., Lindzen, M., Scanzano, R., Aizman, R., Fuzesi, M., Goldshleger, R., Farman, N., Blostein, R., and Karlish, S. J. D. (2002). Am. J. Physiol. 283, F607–F615.Google Scholar
  16. Geering, K. (2001). J. Bioenerg. Biomembr. 33, 425–438.CrossRefGoogle Scholar
  17. Grzmil, M., Voigt, S., Thelen, P., Hemmerlein, B., Helmke, K., and Burfeind, P. (2004). Int. J. Oncol. 24, 97–105.Google Scholar
  18. Hebert, H., Purhonen, P., Vorum, H., Thomsen, K., and Maunsbach, A. B. (2001). J. Mol. Biol. 314, 479–494.CrossRefGoogle Scholar
  19. Kowdley, G. C., Ackerman, S. J., Chen, Z. H., Szabo, G., Jones, L. R., and Moorman, J. R. (1997). Biophys. J. 72, 141–145.CrossRefGoogle Scholar
  20. Kuster, B., Shainskaya, A., Pu, H. X., Goldshleger, R., Blostein, R., Mann, M., and Karlish, S. J. (2000). J. Biol. Chem. 275, 18441–18446.CrossRefGoogle Scholar
  21. Li, C., Grosdidier, A., Crambert, G., Horisberger, J.-D., Michielin, O., and Geering, K. (2004). J. Biol. Chem. 279, 38895–38902.CrossRefGoogle Scholar
  22. Mahmmoud, Y. A., Cramb, G., Maunsbach, A. B., Cutler, C. P., Meischke, L., and Cornelius, F. (2003). J. Biol. Chem. 278, 37427–37438.CrossRefGoogle Scholar
  23. Maxwell, P. J., Longley, D. B., Latif, T., Boyer, J., Allen, W., Lynch, M., McDermott, U., Harkin, D. P., Allegra, C. J., and Johnston, P. G. (2003). Cancer Res. 63, 4602–4606.Google Scholar
  24. Meij, I. C., Koenderink, J. B., van Bokhoven, H., Assink, K. F., Groenestege, W. T., de Pont, J. J., Bindels, R. J., Monnens, L. A., van den Heuvel, L. P., and Knoers, N. V. (2000). Nat. Genet. 26, 265–266.CrossRefGoogle Scholar
  25. Mercer, R. W., Biemesderfer, D., Bliss, D. P., Collins, J. H., and Forbush, B. (1993). J. Cell Biol. 121, 579–586.CrossRefGoogle Scholar
  26. Mirza, M. A., Zhang, X.-Q., Ahlers, B. A., Qureshi, A., Carl, L. L., Song, J., Tucker, A. L., Mounsey, J. P., Moorman, J. R., Rothblum, L. I., Zhang, T. S., and Cheung, J. Y. (2004). Am. J. Physiol. 286, H1322–H1330.Google Scholar
  27. Moorman, J. R., Ackerman, S. J., Kowdley, G. C., Griffin, M. P., Mounsey, J. P., Chen, Z. H., Cala, S. E., Obrian, J. J., Szabo, G., and Jones, L. R. (1995). Nature 377, 737– 740.CrossRefGoogle Scholar
  28. Morrison, B. W., and Leder, P. (1994). Oncogene 9, 3417–3426.Google Scholar
  29. Morrison, B. W., Moorman, J. R., Kowdley, G. C., Kobayashi, Y. M., Jones, L. R., and Leder, P. (1995). J. Biol. Chem. 270, 2176– 2182.CrossRefGoogle Scholar
  30. Palmer, C. J., Scott, B. T., and Jones, L. R. (1991). J. Biol. Chem. 266, 11126–11130.Google Scholar
  31. Pu, H. X., Cluzeaud, F., Goldshlegger, R., Karlish, S. J. D., Farman, N., and Blostein, R. (2001). J. Biol. Chem. 276, 20370–20378.CrossRefGoogle Scholar
  32. Shi, H., Levy-Holzman, R., Cluzeaud, F., Farman, N., and Garty, H. (2001). Am. J. Physiol. 280, F505–F512.Google Scholar
  33. Sweadner, K. J., and Rael, E. (2000). Genomics 68, 41–56.CrossRefGoogle Scholar
  34. Yamaguchi, F., Yamaguchi, K., Tai, Y., Sugimoto, K., and Tokuda, M. (2001). Brain Res. Mol. Brain Res. 86, 189–192.CrossRefGoogle Scholar
  35. Zhang, X.-Q., Qureshi, A., Song, J., Carl, L. L., Tian, Q., Stahl, R. C., Carey, D. J., Rothblum, L. I., and Cheung, J. Y. (2003). Am. J. Physiol. 284, H225–H233.Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Pharmacology and ToxicologyUniversity of LausanneLausanneSwitzerland

Personalised recommendations