Post-Translational Modifications of Eye Lens Crystallins: Crosslinking, Phosphorylation and Deamidation

  • W. W. de Jong
  • J. W. M. Mulders
  • C. E. M. Voorter
  • G. A. M. Berbers
  • W. A. Hoekman
  • H. Bloemendal
Part of the Advances in Experimental Medicine and Biology book series (NATO ASI F, volume 231)


Our knowledge of the structural and functional effects of post-translational modifications of proteins is still fragmentary. It is in general implicitly assumed that such modifications must have important biological roles, in the regulation of enzyme activities, protein interactions or turnover. Although such functions seem plausible in many instances, definite proof is often difficult to provide, and in fact it cannot be excluded that certain modifications are functionally unimportant and just occur as innoxious by-products of the intracellular metabolism. For a better understanding of the meaning of post-translational modifications it is important to analyze and compare their occurrence and features in different proteins and cell types. This contribution reports some recent findings on post-translational modifications of eye lens proteins.


Lens Protein Bovine Lens Argininosuccinate Lyase Rabbit Lens Lens Homogenate 
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.


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  1. 1.
    H. Bloemendal, ed., Molecular and Cellular Biology of the Eye Lens, John Wiley, New York (1981).Google Scholar
  2. 2.
    H. Maisel, ed., The Ocular Lens, Marcel Dekker, New York (1985).Google Scholar
  3. 3.
    J.S. Zigler, and J. Goosey, Aging of protein molecules: lens crystallins as a model system, Trends Biochem. Sci. 6:133 (1981).CrossRefGoogle Scholar
  4. 4.
    H.J. Hoenders, and H. Bloemendal, Lens proteins and aging J. Gerontol. 38:278 (1985).CrossRefGoogle Scholar
  5. 5.
    S. Zigman, Photobiology of the lens, in: H. Maisel, ed., The Ocular Lens, Marcel Dekker, New York, p. 301 (1985).Google Scholar
  6. 6.
    J.J. Harding and M.J.C. Crabbe, The lens: development, proteins, metabolism and cataract, in: H. Davson, ed., The Eye, 3rd Ed. Academic Press, London, p. 207 (1984).CrossRefGoogle Scholar
  7. 7.
    A. Spector, Aspects of the biochemistry of cataract, in: H. Maisel, ed., The Ocular Lens, Marcel Dekker, New York, p. 405 (1985).Google Scholar
  8. 8.
    P.D. Lampe, M.D. Bazzi, G.L. Nelsestuen, and R.G. Johnson, Phosphorylation of lens intrinsic membrane proteins by protein kinase C, Eur J. Biochem. 156:351 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    L. Takemoto, M. Takehana, and J. Horwitz, Covalent changes in MIP26K during aging of the human lens membrane, Invest. Opthalmol. Vis. Sci. 27:443 (1986).Google Scholar
  10. 10.
    A.A. Bouman, A.L.M. de Leeuw, E.F.J. Tolhuizen, and R.M. Broekhuyse, Lens membranes VI. Some characteristics of the EDTA-extractable protein (EEP) from bovine lens fiber membranes, Exp. Eye Res. 29:83 (1979).PubMedCrossRefGoogle Scholar
  11. 11.
    P. Russell, P. Zelenka, T. Martensen, and T.W. Reid, Identification of the EDTA-extractable protein in lens as calpactin I, Curr. Eye Res. 6:533 (1987).PubMedCrossRefGoogle Scholar
  12. 12.
    C.J.M. Saris, B.F. Tack, T. Kirstensen, J.R. Glenney, Jr., and T. Hunter, The cDNA sequence for the protein-tyrosine kinase substrate p36 (calpactin I heavy chain) reveals a multidomain protein with internal repeats, Cell 46:201 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    R.M. Clayton, J.C. Jeanny, D.J. Bower, and L.H. Errington, The presence of extralenticular crystallins and its relationship with transdifferentiation to lens, Curr. Topics Dev. Biol. 20:137 (1986).Google Scholar
  14. 14.
    G.J. Wistow, J.W.M. Mulders, and W.W. de Jong, The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses, Nature 326:622 (1987).PubMedCrossRefGoogle Scholar
  15. 15.
    G.J. Wistow, and J. Piatigorsky, Recruitment of enzymes as lens structural proteins. Science (in press).Google Scholar
  16. 16.
    W.W. de Jong, and W. Hendriks, The eye lens crystallins: ambiguity as evolutionary strategy, J. Mol. Evol. 24:121 (1986).PubMedCrossRefGoogle Scholar
  17. 17.
    H.P.C. Driessen, P. Herbrink, H. Bloemendal, and W.W. de Jong, Primary structure of the bovine β-crystallin Bp chain. Internal duplication and homology with γ-crystallin, Eur. J. Biochem. 121:83 (1981).PubMedCrossRefGoogle Scholar
  18. 18.
    C. Slingsby, Structural variation in lens crystallins, Trends Biochem. Sci. 10:281 (1985).CrossRefGoogle Scholar
  19. 19.
    G. Wistow, L. Summers, and T. Blundell, Myxococcus xanthus spore coat protein S may have a similar structure to vertebrate lens βγ-crystallins, Nature 316:771 (1985).CrossRefGoogle Scholar
  20. 20.
    L. Lorand, L.K.H. Hsu, G.E. Siefring, and N.S. Rafferty, Lens transglutaminase and cataract formation, Proc. Natl. Acad. Sci. USA 78:1356 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    L. Lorand, S.M. Conrad, and P.T. Velasco, Formation of a 55000-weight cross-linked β-crystallin dimer in the Ca2+-treated lens. A model for cataract, Biochem. 24:1525 (1985).CrossRefGoogle Scholar
  22. 22.
    G.A.M. Berbers, W.A. Hoekman, H. Bloemendal, W.W. de Jong, T. Kleinschmidt, and G. Braunitzer, Homology between the primary structures of the major bovine β-crystallin chains, Eur. J. Biochem. 139:467 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    G.A.M. Berbers, R.W. Feenstra, R. van den Bos, W.A. Hoekman, H. Bloemendal, and W.W. de Jong, Lens transglutaminase selects specific β-crystallin sequences as substrate, Proc. Natl. Acad. Sci. USA 81:7017 (1984).PubMedCrossRefGoogle Scholar
  24. 24.
    J.W.M. Mulders, W.A. Hoekman, H. Bloemendal, and W.W. de Jong, βB1-Crystallin is an amine-donor substrate for tissue transglutaminase, Exp. Cell Res. (in press).Google Scholar
  25. 245.
    G.E. Siefring, A.B. Apostol, P.T. Velasco, and L. Lorand, Enzymatic basis for the Ca2+-induced cross-linking of membrane proteins in intact human erythrocytes, Biochemistry 17:2598 (1978).PubMedCrossRefGoogle Scholar
  26. 26.
    P.J. Birckbichler, G.R. Orr, M.K. Patterson, E. Conway, and H.A. Carter, Increase in proliferative markers after inhibition of transglutaminase, Proc. Natl. Acad. Sci. USA 78:5005 (1981).PubMedCrossRefGoogle Scholar
  27. 27.
    F.S.M. van Kleef, W.W. de Jong, and H.J. Hoenders, Stepwise degradations and deamidation of the eye lens protein α-crystallin in ageing. Nature 258:264 (1975).PubMedCrossRefGoogle Scholar
  28. 28.
    A. Spector, R. Chiesa, J. Sredy, and W. Garner, cAMP-dependent phosphorylation of bovine lens a-crystallin, Proc. Natl. Acad. Sci. USA 82:4712 (1985).PubMedCrossRefGoogle Scholar
  29. 29.
    C.E.M. Voorter, J.W.M. Mulders, H. Bloemendal, and W.W. de Jong, Some aspects of the phosphorylation of a-crystallin A, Eur. J. Biochem. 160:203 (1986).PubMedCrossRefGoogle Scholar
  30. 30.
    R. Chiesa, M.A. Gawinowicz-Kolks, N.J. Kleiman, and A. Spector, Identification of the specific phosphorylated serine in the bovine alpha crystallin A1 chain, Curr. Eye Res. 6:539 (1987).PubMedCrossRefGoogle Scholar
  31. 31.
    E.G. Krebs, and J.A. Beavo, Phosphorylation-dephosphorylation of enzymes, Annu. Rev. Biochem. 48:923 (1979).PubMedCrossRefGoogle Scholar
  32. 32.
    E. Hickey, S.E. Brandon, R. Potter, G. Stein, and L.A. Weber, Sequence and organization of genes encoding the human 27 kDa heat shock protein, Nucl. Acids Res. 14:4127 (1986).PubMedCrossRefGoogle Scholar
  33. 33.
    W.W. de Jong, E.C. Terwindt, and G. Groenewoud, Subunit compositions of vertebrate α-crystallins, Comp. Biochem. Physiol. 55B:49 (1976).Google Scholar
  34. 34..
    C.E.M. Voorter, E.S. Roersma, H. Bloemendal, and W.W. de Jong, Age-dependent deamidation of chicken αA-crystallin, (submitted for publication).Google Scholar
  35. 35.
    W.W. de Jong, A. Zweers, M. Versteeg, and E.C. Nuij-Terwindt, Primary structures of a-crystallin A chains of twenty-eight mammalian species, chicken and frog, Eur. J. Biochem. 141:131 (1984).PubMedCrossRefGoogle Scholar
  36. 36.
    M.A. Thompson, J.W. Hawkins, and J. Piatigorsky, Complete nucleotide sequence of the chicken αA-crystallin gene and its 5’ flanking region, Gene (in press).Google Scholar
  37. 37.
    A.B. Robinson and C.J. Rudd, Deamidation of glutaminyl and asperaginyl residues in peptides and proteins, Curr. Topics Cell. Regul. 8:247 (1974).Google Scholar
  38. 38.
    J. Piatigorsky, Gene expression and genetic engineering in the lens, Invest. Ophthalmol. Vis. Sci. 28:9 (1987).PubMedGoogle Scholar
  39. 39.
    J.A. Kramps, W.W. de Jong, J. Wollensak, and H.J. Hoenders, The polypeptide chains of a-crystallin from old human eye lenses, Blochim. Biophys. Acta 533:487 (1978).CrossRefGoogle Scholar
  40. 40.
    S. Clarke, Protein carboxyl methyltransferases: two distinct classes of enzymes, Annu. Rev. Biochem. 54:479 (1985).PubMedCrossRefGoogle Scholar
  41. 41.
    P.N. McFadden, and S. Clarke, Protein carboxyl methyltransferase and methyl acceptor proteins in the human eye lens, Mech. Ageing Dev. 34:91 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • W. W. de Jong
    • 1
  • J. W. M. Mulders
    • 1
  • C. E. M. Voorter
    • 1
  • G. A. M. Berbers
    • 1
  • W. A. Hoekman
    • 1
  • H. Bloemendal
    • 1
  1. 1.Dept. of Biochemistry, Centre of Eye ResearchUniv. of NijmegenNijmegenThe Netherlands

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