Advertisement

Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 6, pp 1265–1274 | Cite as

Malformation of junctional microdomains in cataract lens membranes from a type II diabetes patient

  • Stéphanie Mangenot
  • Nikolay Buzhynskyy
  • Jean-François Girmens
  • Simon Scheuring
Ion Channels, Receptors and Transporters

Abstract

In eye core lens membranes, aquaporin-0 (AQP0) and connexins (Cx) form together well-structured supramolecular assemblies, the junctional microdomains, in which they assure water, ion, metabolite, and waste transport. Additionally, they mediate cell–cell adhesion-forming thin junctions (AQP0) and gap junctions (Cx). We have used atomic force microscopy and biochemical methods to analyze and compare the structure of junctional microdomains in human cataract lens membranes from a type II diabetes patient and healthy lens membranes from calf. A healthy intercellular junctional microdomain consists in average of ∼150 tetragonally arranged (a = b = 65.5 Å, γ = 90°) AQP0 tetramers surrounded by densely packed non-ordered connexon channels. Gap-junction connexons act as lineactants inside the membrane and confine AQP0 in the junctional microdomains. In the diabetic cataract lens, connexons were degraded, and AQP0 arrays are malformed. We conceptualize that absence of connexons lead to breakdown of cell nutrition.

Keywords

Aquaporin-0 Atomic force microscopy Connexin Connexon Gap junction Membrane protein Membrane structure 

Notes

Acknowledgements

This study was supported by the ‘ANR-06-NANO-023’, a ‘Nanosciences Ile-de-France’ and a ‘bourse de recherche médicale 2007 de la Ville de Paris’ grants. The MALDI-TOF analysis was performed in the ‘Laboratoire de Spectrométrie de Masse, Institut Curie’ with the kind help of Dr. W. Faigle. The calf lenses were supplied by Dr. A. Tardieu. We thank the patient for giving the permission to analyze the surgery debris.

References

  1. 1.
    Bloemendal H (1981) Molecular and cellular biology of the eye lens. Wiley, New YorkGoogle Scholar
  2. 2.
    Donaldson P, Kistler J, Mathias RT (2001) Molecular solutions to mammalian lens transparency. News Physiol. Sci. 16:118–123 DOI Electronic Resource NumberPubMedGoogle Scholar
  3. 3.
    Andley U (2007) Crystallins in the eye: function and pathology. Prog Retin Eye Res 25:78–98 DOI Electronic Resource NumberCrossRefGoogle Scholar
  4. 4.
    Alcala J, Lieska N, Maisel H (1975) Protein composition of bovine lens cortical fiber cell membranes. Exp Eye Res 21:581–595 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  5. 5.
    Gonen T, Cheng Y, Kistler J, Walz T (2004) Aquaporin-0 membrane junctions form upon proteolytic cleavage. J Mol Biol 342:1337–1345 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  6. 6.
    Fleschner C, Cenedella R (1991) Lipid composition of lens plasma membrane fractions enriched in fiber junctions. J Lipid Res 32:45–53 DOI Electronic Resource NumberPubMedGoogle Scholar
  7. 7.
    Shiels A, Bassnett S (1996) Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nature Genet. 12:212–215 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  8. 8.
    www.WHO.int (2007) Diabetes Programme
  9. 9.
    Wild S, Roglic G, Green A, Sicree R, King H (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–53 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  10. 10.
    Binnig G, Quate CF, Gerber C (1986) Atomic force microscope. Phys Rev Lett 56:930–933 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  11. 11.
    Schabert FA, Henn C, Engel A (1995) Native Escherichia coli OmpF porin surfaces probed by atomic force microscopy. Science 268:92–94 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  12. 12.
    Seelert H, Poetsch A, Dencher NA, Engel A, Stahlberg H, Müller DJ (2000) Proton powered turbine of a plant motor. Nature 405:418–419 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  13. 13.
    Scheuring S, Seguin J, Marco S, Levy D, Robert B, Rigaud J-L (2003) Nanodissection and high-resolution imaging of the Rhodopseudomonas viridis photosynthetic core-complex in native membranes by AFM. Proc Natl Acad Sci 100:1690–1693 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  14. 14.
    Scheuring S, Sturgis JN, Prima V, Bernadac A, Lévy D, Rigaud J-L (2004) Watching the photosynthetic apparatus in native membranes. Proc Natl Acad Sci USA 101:11293–11297 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  15. 15.
    Scheuring S, Busselez J, Levy D (2005) Structure of the dimeric PufX–containing core complex of Rhodobacter blasticus by in situ AFM. J Biol Chem 180:1426–1431 DOI Electronic Resource NumberGoogle Scholar
  16. 16.
    Scheuring S, Sturgis JN (2005) Chromatic adaptation of photosynthetic membranes. Science 309:484–487 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  17. 17.
    Gonçalves RP, Bernadac A, Sturgis JN, Scheuring S (2005) Architecture of the native photosynthetic apparatus of Phaeospirillum molischianum. J Struct Biol 152:221–228 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  18. 18.
    Scheuring S, Gonçalves RP, Prima V, Sturgis JN (2006) The photosynthetic apparatus of Rhodopseudomonas palustris: structures and organization. J Mol Biol 358:83–96 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  19. 19.
    Bahatyrova S, Frese RN, Siebert CA, Olsen JD, Van Der Werf KO, van Grondelle R, Niederman RA, Bullough PA, Hunter CN (2004) The native architecture of a photosynthetic membrane. Nature 430:1058–1062 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  20. 20.
    Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2003) Atomic-force microscopy: Rhodopsin dimers in native disc membranes. Nature 421:127–128 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  21. 21.
    Buzhynskyy N, Sens P, Prima V, Sturgis JN, Scheuring S (2007) Rows of ATP synthase dimers in native mitochondrial inner membranes. Biophys J 93:2870–2876 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  22. 22.
    Gonçalves RP, Buzhynskyy N, Prima V, Sturgis JN, Scheuring S (2007) Supramolecular assembly of VDAC in native mitochondrial outer membranes. J Mol Biol 369:413–418 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  23. 23.
    Buzhynskyy N, Hite RK, Walz T, Scheuring S (2007) The supramolecular architecture of junctional microdomains in native lens membranes. EMBO Reports 8:51–55 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  24. 24.
    Scheuring S, Buzhynskyy N, Jaroslawski S, Gonçalves RP, Hite RK, Walz T (2007) Structural models of the supramolecular organization of AQP0 and connexons in junctional microdomains. J Struct Biol 160:385–394 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  25. 25.
    Buzhynskyy N, Girmens J-F, Faigle W, Scheuring S (2007) Human cataract lens membrane at subnanometer resolution. J Mol Biol 374:162–169 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  26. 26.
    Gonen T, Sliz P, Kistler J, Cheng Y, Walz T (2004) Aquaporin-0 membrane junctions reveal the structure of a closed water pore. Nature 13:193–197 DOI Electronic Resource NumberCrossRefGoogle Scholar
  27. 27.
    Harries WE, Akhavan D, Miercke LJ, Khademi S, Stroud RM (2004) The channel architecture of aquaporin 0 at a 2.2-A resolution. Proc Natl Acad Sci 101:14045–14050 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  28. 28.
    Gonen T, Cheng Y, Sliz P, Hiroaki Y, Fujiyoshi Y, Harrison SC, Walz T (2005) Lipid–protein interactions in double-layered two-dimensional AQP0 crystals. Nature 438:633–638 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  29. 29.
    Unger V, Kumar N, Gilula N, Yaeger M (1999) Three-dimensional structure of a recombinant gap junction membrane channel. Science 283:1176–1180 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  30. 30.
    Riley M, Harding J, Kilby G, Truscott R, Aquilina A, Sheil M (1996) Molecular masses of gamma-crystallins. Ophthalmic Res 28:131–135 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  31. 31.
    Fan J, Donovan A, Ledee D, Zelenka P, Fariss R, Chepelinsky A (2004) gammaE-crystallin recruitment to the plasma membrane by specific interaction between lens MIP/aquaporin-0 and gammaE-crystallin. Invest Ophthalmol Vis Sci 45:863–871 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  32. 32.
    Yu X, Jiang J (2004) Interaction of major intrinsic protein (aquaporin-0) with fiber connexins in lens development. J Cell Science 117:871–880 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  33. 33.
    Zampighi G, Simon SA, Robertson JD, McIntosh TJ, Costello MJ (1982) On the structural organization of isolated bovine lens fiber junctions. J. Cell Biol. 93:175–189 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  34. 34.
    Zampighi GA, Eskandari S, Hall JE, Zampighi L, Kreman M (2002) Micro-domains of AQP0 in lens equatorial fibers. Exp. Eye Res. 75:505–519 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  35. 35.
    Ball LE, Little M, Nowak MW, Garland DL, Crouch RK, Schey KL (2003) Water permeability of C-terminally truncated aquaporin 0 (AQP0 1–243) Observed in the Aging Human Lens. Invest Ophthalmol Vis Sci 44:4820–4828 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  36. 36.
    Gonen T, Hite RK, Cheng Y, Petre BM, Kistler J, Walz T (2008) Polymorphic assemblies and crystalline arrays of lens tetraspanin MP20. J Mol Biol 376:380–392 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  37. 37.
    Fielding C (2006) Lipid rafts and caveolae: from membrane biophysics to cell biology. Wiley, Weinheim, GermanyGoogle Scholar
  38. 38.
    Sorbo JG, Moe SE, Ottersen OP, Holen T (2008) The Molecular composition of square arrays. Biochemistry 47:2631–2637 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  39. 39.
    Laemmli UK (1970) Cleavage of structural proteins during assembly of the head of bacteriophage T4. Nature 227:680–685 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  40. 40.
    Scheuring S, Boudier T, Sturgis JN (2007) From high-resolution AFM topographs to atomic models of supramolecular assemblies. J Struct Biol 159:268–276 DOI Electronic Resource NumberPubMedCrossRefGoogle Scholar
  41. 41.
    Rasband WS (1997–2005) ImageJ. U.S. National Institutes of Health, Bethesda, Maryland, USA, http://rsb.info.nih.gov/ij/ Resource Number
  42. 42.
    DeLano WL (2002) The PyMOL Molecular Graphics System, http://www.pymol.org. Resource Number

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Stéphanie Mangenot
    • 1
    • 2
  • Nikolay Buzhynskyy
    • 1
  • Jean-François Girmens
    • 3
  • Simon Scheuring
    • 1
  1. 1.Institut Curie, Équipe INSERM Avenir, UMR168-CNRSParis Cedex 05France
  2. 2.Université Paris-SudOrsay CedexFrance
  3. 3.Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Service IV & CICParis Cedex 12France

Personalised recommendations