Nuclear Envelope: Nanoarray Responsive to Aldosterone

  • Hans Oberleithner


In 1994 a paper was published that contained a rather unusual observation made with a rather unusual technique (Oberleithner et al. 1994). The unusual observation was the increase in number of nuclear pore complexes (NPCs) in nuclear envelopes of kidney cells in response to aldosterone and the unusual technique applied in this study was atomic force microscopy (AFM). At that time, aldosterone had been considered as a hormone that controlled fluid and electrolyte balance in kidney through regulation of plasma membrane ion channels and transporters but virtually nothing was known about its interaction with the nuclear barrier. Possibly, those AFM experiments were born of the desperate desire of a few renal physiologists who wanted to apply a new nanotechnique, originally developed by physicists working in the material sciences (Binnig and Quate 1986), on a biological membrane with some relevance for kidney function. In the meantime 10 years have passed. Aldosterone underwent a dazzling metamorphosis in terms of site and mode of action (Oberleithner 2004). Atomic force microscopy developed into a useful tool in the biological sciences (Roco 2003). Finally, the nuclear envelope advanced to an extensively explored membrane system that selectively passes signals from outside into the nucleus (Gerasimenko et al. 2003). In this short review chapter I will focus on recent developments in this field


Atomic Force Microscopy Human Umbilical Vein Endothelial Cell Nuclear Envelope Mineralocorticoid Receptor Central Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alzamora R, Michea L, Marusic ET (2000) Role of 11 beta-hydroxysteroid dehydrogenase in nongenomic aldosterone effects in human arteries. Hypertension 35:1099–1104PubMedGoogle Scholar
  2. Arriza JL, Weinberger C, Cerelli G, Glaser TM, Handelin BL, Housman, DE, Evans RM (1987) Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science 237:268–275PubMedCrossRefGoogle Scholar
  3. Berge T, Ellis DJ, Dryden DT, Edwardson JM, Henderson RM (2000) Translocation-independent dimerization of the EcoKI endonuclease visualized by atomic force microscopy. Biophys J 79:479–484PubMedGoogle Scholar
  4. Binnig G, Quate CF (1986) Atomic force microscope. Phys Rev Lett 56(9):930–934PubMedCrossRefGoogle Scholar
  5. Buchholz I, Enss K, Schafer C, Shahin V, Albermann L, Schlune A, Oberleithner H (2004) Transient permeability leak of nuclear envelope induced by aldosterone. J Membr Biol. 199:135–141PubMedCrossRefGoogle Scholar
  6. Bustamante JO, Hanover JA, Liepins A (1995) The ion channel behavior of the nuclear pore complex. J Membr Biol 146:239–251PubMedGoogle Scholar
  7. Couette B, Fagart J, Jalaguier S, Lombes M, Souque A, Rafestin-Oblin ME (1996) Ligand-induced conformational change in the human mineralocorticoid receptor occurs within its hetero-oligomeric structure. Biochem J 315 (Pt 2):421–427PubMedGoogle Scholar
  8. Danker T, Schillers H, Storck J, Shahin V, Kramer B, Wilhelmi M, Oberleithner H (1999) Nuclear hourglass technique: novel approach detects electrically open pores in Xenopus laevis oocyte. Proc Natl Acad Sci USA 96:13531–13535CrossRefGoogle Scholar
  9. Delyani JA (2000) Mineralocorticoid receptor antagonists: the evolution of utility and pharmacology. Kidney Int 57:1408–1411PubMedCrossRefGoogle Scholar
  10. Epstein M (2001) Aldosterone and the hypertensive kidney: its emerging role as a mediator of progressive renal dysfunction: a paradigm shift. J Hypertens 19:829–842PubMedCrossRefGoogle Scholar
  11. Falkenstein E, Christ M, Feuring M, Wehling M (2000) Specific nongenomic actions of aldosterone. Kidney Int 57:1390–1394PubMedCrossRefGoogle Scholar
  12. Fejes-Toth G, Pearce D, Naray-Fejes-Toth A (1998) Subcellular localization of mineralocorticoid receptors in living cells: effects of receptor agonists and antagonists. Proc Natl Acad Sci USA 95:2973–2978PubMedCrossRefGoogle Scholar
  13. Funder JW (2001) Non-genomic actions of aldosterone: role in hypertension. Curr Opin Nephrol Hypertens 10:227–230PubMedCrossRefGoogle Scholar
  14. Gekle M, Golenhofen N, Oberleithner H, Silbernagl S (1996) Rapid activation of Na+/H+ exchange by aldosterone in renal epithelial cells requires Ca2+ and stimulation of a plasma membrane proton conductance. Proc Natl Acad Sci USA 93:10500–10504PubMedCrossRefGoogle Scholar
  15. Gerasimenko J, Maruyama Y, Tepikin A, Petersen OH, Gerasimenko O (2003) Calcium signalling in and around the nuclear envelope. Biochem Soc Trans 31:76–78PubMedCrossRefGoogle Scholar
  16. Golden L, Schafer U, Rosbash M (1980) Accumulation of individual pA+ RNAs during oogenesis of Xenopus laevis. Cell 22:835–844PubMedCrossRefGoogle Scholar
  17. Golestaneh N, Klein C, Valamanesh F, Suarez G, Agarwal MK, Mirshahi M (2001) Mineralocorticoid receptor-mediated signaling regulates the ion gated sodium channel in vascular endothelial cells and requires an intact cytoskeleton. Biochem Biophys Res Commun 280:1300–1306PubMedCrossRefGoogle Scholar
  18. Harvey BJ, Higgins M (2000) Nongenomic effects of aldosterone on Ca2+ in M-l cortical collecting duct cells. Kidney Int 57:1395–1403PubMedCrossRefGoogle Scholar
  19. Hatakeyama H, Miyamori I, Fujita T, Takeda Y, Takeda R, Yamamoto H (1994) Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells. J Biol Chem 269:24316–24320PubMedGoogle Scholar
  20. Hayashi H, Szaszi K, Grinstein S (2002) Multiple modes of regulation of Na+/H+ exchangers. Ann N Y Acad Sci 976:248–258PubMedCrossRefGoogle Scholar
  21. Henderson RM, Oberleithner H (2000) Pushing, pulling, dragging, and vibrating renal epithelia by using atomic force microscopy. Am J Physiol Renal Physiol 278:F689–F701PubMedGoogle Scholar
  22. Henderson RM, Schneider S, Li Q, Hornby D, White SJ, Oberleithner H (1996) Imaging ROMK1 inwardly rectifying ATP-sensitive K+ channel protein using atomic force microscopy. Proc Natl Acad Sci USA 93:8756–8760PubMedCrossRefGoogle Scholar
  23. Hinshaw JE, Carragher BO, Milligan RA (1992) Architecture and design of the nuclear pore complex. Cell 69:1133–1141PubMedCrossRefGoogle Scholar
  24. Jalaguier S, Mornet D, Mesnier D, Leger JJ, Auzou G (1996) Human mineralocorticoid receptor interacts with actin under mineralocorticoid ligand modulation. FEBS Lett 384:112–116PubMedCrossRefGoogle Scholar
  25. Leonard DA, La Marca MJ (1975) In vivo synthesis and turnover of cytoplasmic ribosomal RNA by stage 6 oocytes of Xenopus laevis. Dev Biol 45:199–202PubMedCrossRefGoogle Scholar
  26. Mazzanti M, Bustamante JO, Oberleithner H (2001) Electrical dimension of the nuclear envelope. Physiol Rev 81:1–19PubMedGoogle Scholar
  27. Mihailidou AS, Bundgaard H, Mardini M, Hansen PS, Kjeldsen K, Rasmussen HH (2000) Hyperaldosteronemia in rabbits inhibits the cardiac sarcolemmal Na(+)-K(+) pump. Circ Res 86:37–42PubMedGoogle Scholar
  28. Oberleithner H (2004) Unorthodox sites and modes of aldosterone action. News Physiol Sci 19:51–54PubMedGoogle Scholar
  29. Oberleithner H, Brinckmann E, Schwab A, Krohne G (1994) Imaging nuclear pores of aldosterone sensitive kidney cells by atomic force microscopy. Proc Natl Acad Sci USA 91:9784–9788PubMedCrossRefGoogle Scholar
  30. Oberleithner H, Reinhardt J, Schillers H, Pagel P, Schneider SW (2000) Aldosterone and nuclear volume cycling. Cell Physiol Biochem 10:429–434PubMedCrossRefGoogle Scholar
  31. Oberleithner H, Schneider SW, Albermann L, Hillebrand U, Ludwig T, Riethmuller C, Shahin V, Schafer C, Schillers H (2003) Endothelial cell swelling by aldosterone. J Membr Biol 196:163–172PubMedCrossRefGoogle Scholar
  32. Oberleithner H, Ludwig T, Riethmuller C, Hillebrand U, Albermann L, Schafer C, Shahin V, Schillers H (2004) Human endothelium: target for aldosterone. Hypertension 43:952–956PubMedCrossRefGoogle Scholar
  33. Pietrasanta LI, Thrower D, Hsieh W, Rao S, Stemmann O, Lechner J, Carbon J, Hansma H (1999) Probing the Saccharomyces cerevisiae centromeric DNA (CEN DNA)-binding factor 3 (CBF3) kinetochore complex by using atomic force microscopy. Proc Natl Acad Sci USA 96:3757–3762PubMedCrossRefGoogle Scholar
  34. Roco MC (2003) Nanotechnology: convergence with modern biology and medicine. Curr Opin Biotechnol 14:337–346PubMedCrossRefGoogle Scholar
  35. Schafer C, Shahin V, Albermann L, Hug MJ, Reinhardt J, Schillers H, Schneider SW, Oberleithner H (2002) Aldosterone signaling pathway across the nuclear envelope. Proc Natl Acad Sci USA 99:7154–7159PubMedCrossRefGoogle Scholar
  36. Schafer C, Shahin V, Albermann L, Schillers H, Hug MJ, Oberleithner H (2003) Intracellular calcium: a prerequisite for aldosterone action. J Membr Biol 196:157–162PubMedCrossRefGoogle Scholar
  37. Schneider M, Ulsenheimer A, Christ M, Wehling M (1997a) Nongenomic effects of aldosterone on intracellular calcium in porcine endothelial cells. Am J Physiol 272:E616–E620PubMedGoogle Scholar
  38. Schneider SW, Yano Y, Sumpio BE, Jena BP, Geibel JP, Gekle M, Oberleithner H (1997b) Rapid aldosterone-induced cell volume increase of endothelial cells measured by the atomic force microscope. Cell Biol Int 21:759–768PubMedCrossRefGoogle Scholar
  39. Schneider SW, Larmer J, Henderson RM, Oberleithner H (1998) Molecular weights of individual proteins correlate with molecular volumes measured by atomic force microscopy [In Process Citation]. Pflügers Arch 435:362–367PubMedCrossRefGoogle Scholar
  40. Shahin V, Danker T, Enss K, Ossig R, Oberleithner H (2001) Evidence for Ca2+-and ATP-sensitive peripheral channels in nuclear pore complexes. FASEB J 15:1895–1901PubMedCrossRefGoogle Scholar
  41. Silvestre JS, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic JM, Swynghedauw B, Delcayre C (1998) Myocardial production of aldosterone and corticosterone in the rat. Physiological regulation. J Biol Chem 273:4883–4891PubMedCrossRefGoogle Scholar
  42. Sperling R, Koster AJ, Melamed-Bessudo C, Rubinstein A, Angenitzki M, Berkovitch-Yellin Z, Sperling J (1997) Three-dimensional image reconstruction of large nuclear RNP (lnRNP) particles by automated electron tomography. J Mol Biol 267:570–583PubMedCrossRefGoogle Scholar
  43. Symons JD, Schaefer S (2001) Na(+)/H(+) exchange subtype 1 inhibition reduces endothelial dysfunction in vessels from stunned myocardium. Am J Physiol Heart Circ Physiol 281:H1575–H1582PubMedGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Hans Oberleithner
    • 1
  1. 1.Institute of Physiology II, NanolabUniversity MünsterMünsterGermany

Personalised recommendations