The eye lens cytoskeleton

Abstract

During lens cell differentiation there are a number of very characteristic morphological changes that occur. These include a 50- to 100-fold increase in cell length as the equatorial lens epithelial cells differentiate into fibre cells and the loss of the cellular organelles such as mitochondria, nuclei, Golgi apparatus and endoplasmic reticulum. Coincident with these changes are dramatic alterations in the organisation of the lens fibre cell cytoskeleton and in particular the lens-specific intermediate filament network comprising CP49 and filensin. Cell shape and cell polarisation as well as tissue integrity are all processes that depend upon the cytoskeleton and are therefore important to the lens. The unique aspects of the lenticular cytoskeleton are the subject of this review.

References

  1. 1

    Orii H, Agata K, Sawada K, Eguchi G, Maisel H . Evidence that the chick lens cytoskeletal protein CP49 belongs to the family of intermediate filament proteins. Curr Eye Res 1993;12:583–8.

    CAS  PubMed  Google Scholar 

  2. 2

    Hess JF, Casselman JT, FitzGerald PG . cDNA analysis of the 49 kDa lens fibre cell cytoskeletal protein: a new, lens-specific member of the intermediate filament family? Curr Eye Res 1993;12:77–88.

    CAS  PubMed  Google Scholar 

  3. 3

    Sawada K, Agata J, Eguchi G, Quinlan RA, Maisel H . The predicted structure of CP49 and a variant thereof, CP49ins, the first vertebrate cytoplasmic intermediate filament protein with a lamin-like insertion in helix 1B. Curr Eye Res 1995;14:545–53.

    CAS  PubMed  Google Scholar 

  4. 4

    Wallace P, Signer E, Paton IR, Burt D, Quinlan R . The chicken CP49 gene contains an extra exon compared to the human CP49 gene which identifies an important step in the evolution of the eye lens intermediate filament proteins. Gene 1998;211:19–27.

    CAS  PubMed  Google Scholar 

  5. 5

    Hess JF, Casselman JT, Fitzgerald PG . Gene structure and cDNA sequence identify the beaded filament protein cp49 as a highly divergent type-1 intermediate filament protein. J Biol Chem 1996;271:6729–35.

    CAS  PubMed  Google Scholar 

  6. 6

    Merdes A, Gournari F, Georgatos SD . The 47-kD lens-specific protein phakinin is a tailless intermediate filament protein and an assembly partner of filensin. J Cell Biol 1993;123:1507–16.

    CAS  PubMed  Google Scholar 

  7. 7

    Rendtorff ND, Hansen C, Silahtaroglu A, Henriksen KF, Tommerup N . Isolation of the human beaded-filament structural protein 1 gene (BFSP1) and assignment to chromosome 20pll.23-p12.1. Genomics 1998;53:114–6.

    CAS  PubMed  Google Scholar 

  8. 8

    Masaki S, Watanabe T . cDNA sequence analysis of CP94: rat lens fibre cell beaded-filament structural protein shows homology to cytokeratins. Biochem Biophys Res Commun 1992;186:190–8.

    CAS  PubMed  Google Scholar 

  9. 9

    Masaki S, Quinlan RA . Gene structure and sequence comparisons of the eye lens specific protein, filensin, from rat and mouse: implications for protein classification and assembly. Gene 1997:201:11–20.

    CAS  PubMed  Google Scholar 

  10. 10

    Remington SG . Chicken filensin: a lens fibre cell protein that exhibits sequence similarity to intermediate filament proteins. J Cell Sci 1993;105:1057–68.

    CAS  PubMed  Google Scholar 

  11. 11

    Gounari F, et al. Bovine filensin possesses primary and secondary structure similarity to intermediate filament proteins. J Cell Biol 1993;121:847–53.

    CAS  PubMed  Google Scholar 

  12. 12

    Hess JF, Casselman JT, Kong AP, FitzGerald PG . Primary sequence, secondary structure, gene structure, and assembly properties suggests that the lens-specific cytoskeletal protein filensin represents a novel class of intermediate filament protein. Exp Eye Res 1998;66:625–44.

    CAS  PubMed  Google Scholar 

  13. 13

    FitzGerald PG, Graham D . Ultrastructural localisation of alpha A-crystallin to the bovine lens fibre cell cytoskeleton. Curr Eye Res 1991;10:417–36.

    CAS  PubMed  Google Scholar 

  14. 14

    Carter JM, Hutcheson AM, Quinlan RA . In vitro studies on the assembly properties of the lens beaded filament proteins: co-assembly with α-crystallin but not with vimentin. Exp Eye Res 1995;60:181–92.

    CAS  PubMed  Google Scholar 

  15. 15

    Maisel H, Perry MM . Electron microscope observations on some structural proteins of the chick lens. Exp Eye Res 1972;14:7–12.

    CAS  PubMed  Google Scholar 

  16. 16

    Goulielmos G, et al. Filensin and phakinin form a novel type of beaded intermediate filaments and coassemble de-novo in cultured-cells. J Cell Biol 1996;132:643–55.

    CAS  PubMed  Google Scholar 

  17. 17

    Goulielmos G, Remington S, Schwesinger F, Georgatos SD, Gounari F . Contributions of the structural domains of filensin in polymer formation and filament distribution. J Cell Sci 1996;109:447–56.

    CAS  PubMed  Google Scholar 

  18. 18

    Vicart P, et al. A missense mutation in the alpha B-crystallin chaperone gene causes a desmin-related myopathy. Nature Genet 1998;20:92–5.

    CAS  PubMed  Google Scholar 

  19. 19

    Nicholl ID, Quinlan RA . Chaperone activity of α-crystallins modulates intermediate filament assembly. EMBO J 1994;13:945–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20

    Janmey PA, Euteneuer U, Traub P, Schliwa M . Viscoelastic properties of vimentin compared with other filaments biopolymer networks. J Cell Biol 1991;113:155–60.

    CAS  PubMed  Google Scholar 

  21. 21

    Fuchs E, Cleveland DW . A structural scaffolding of intermediate filaments in health and disease. Science 1998;279:514–9.

    CAS  PubMed  Google Scholar 

  22. 22

    McLean WH, et al. Loss of plectin causes epidermolysis bullosa with muscular dystrophy: cDNA cloning and genomic organisation. Genes Dev 1996;10:1724–35.

    CAS  PubMed  Google Scholar 

  23. 23

    Goldfarb LG, et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nature Genet 1998;19:402–3.

    CAS  PubMed  Google Scholar 

  24. 24

    Munoz-Marmol AM, et al. A dysfunctional desmin mutation in a patient with severe generalised myopathy. Proc Natl Acad Sci USA 1998;95:11312–7.

    CAS  PubMed  Google Scholar 

  25. 25

    Irvine AD, et al. Mutations in cornea-specific keratin K3 or K12 genes cause Meesmann's corneal dystrophy. Nature Genet 1997;16:184–7.

    CAS  PubMed  Google Scholar 

  26. 26

    Litt M, et al. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet 1998;7:471–4.

    CAS  PubMed  Google Scholar 

  27. 27

    Houseweart MK, Cleveland DW . Intermediate filaments and their associated proteins: multiple dynamic personalities. Curr Opin Cell Biol 1998;10:93–101.

    CAS  PubMed  Google Scholar 

  28. 28

    Capetanaki Y, Smith S, Heath JP . Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation. J Cell Biol 1989;109:1653–64.

    CAS  PubMed  Google Scholar 

  29. 29

    Dunia L, et al. Plasma membrane-cytoskeleton damage in eye lenses of transgenic mice expressing desmin. Eur J Cell Biol 1990;53:59–74.

    CAS  PubMed  Google Scholar 

  30. 30

    Monteiro MJ, Hoffman PN, Gearhart JD, Cleveland DW . Expression of NF-L in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber. J Cell Biol 1990;111:1543–57.

    CAS  PubMed  Google Scholar 

  31. 31

    Bloemendal H, Raats JM, Pieper FR, Benedetti EL, Dunia I . Transgenic mice carrying chimeric or mutated type III intermediate filament (IF) genes. Cell Mol Life Sci 1997;53:1–12.

    CAS  PubMed  Google Scholar 

  32. 32

    Becker B, Bellin RM, Sernett SW, Huiatt TW, Robson RM . Synemin contains the rod domain of intermediate filaments. Biochem Biophys Res Commun 1995;213:796–802.

    CAS  PubMed  Google Scholar 

  33. 33

    Hemken PM, et al. Molecular characteristics of the novel intermediate filament protein paranemin: sequence reveals EAP-300 and IFAPa-400 are highly homologous to paranemin. J Biol Chem 1997;272:32489–99.

    CAS  PubMed  Google Scholar 

  34. 34

    Quinlan RA, et al. Characterisation of dimer subunits of intermediate filament proteins. J Mol Biol 1986;192:337–49.

    CAS  PubMed  Google Scholar 

  35. 35

    Söllner P, Quinlan RA, Franke WW . Identification of a distinct soluble subunit of an intermediate filament protein: tetrameric vimentin from living cells. Proc Natl Acad Sci USA 1985;82:7929–33.

    Google Scholar 

  36. 36

    Quinlan RA, Hutcheson C, Lane B . Intermediate filament proteins. Protein Profiles 1995;2:801–952.

    CAS  Google Scholar 

  37. 37

    Quinlan RA, Carter JM, Sandilands A, Prescott AR . The beaded filament of the eye lens: an unexpected key to intermediate filament structure and function. Trends Cell Biol 1996;6:123–6.

    CAS  PubMed  Google Scholar 

  38. 38

    Vikstrom KL, Lim SS, Goldman RD, Borisy GG . Steady state dynamics of intermediate filament networks. J Cell Biol 1992;118:121–9.

    CAS  PubMed  Google Scholar 

  39. 39

    Yoon M, Moir RD, Prahlad V, Goldman RD . Motile properties of vimentin intermediate filament networks in living cells. J Cell Biol 1998;143:147–57.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Geisler N, Weber K . Isolation of assembly competent vimentin from porcine eye lens tissue. FEBS Lett 1981;125:253–6.

    CAS  PubMed  Google Scholar 

  41. 41

    Kasper M, Viebahn C . Cytokeratin expression and early lens development. Anat Embryol Berl 1992;186:285–90.

    CAS  PubMed  Google Scholar 

  42. 42

    Ellis M, Alousi S, Lawniczak J, Maisel H, Welsh M . Studies on lens vimentin. Exp Eye Res 1984;38:195–202.

    CAS  PubMed  Google Scholar 

  43. 43

    Sandilands A, et al. Vimentin and CP49/filensin form distinct networks in the lens which are independently modulated during lens fibre cell differentiation. J Cell Sci 1995;108:1397–406.

    CAS  PubMed  Google Scholar 

  44. 44

    Dahm R, Gribbon C, Quinlan RA, Prescott AR . Changes in the nucleolar and coiled body compartments precede lamina and chromatin reorganisation during fibre cell denucleation in the bovine lens. Eur J Cell Biol 1998;75:237–46.

    CAS  PubMed  Google Scholar 

  45. 45

    Sandilands A, et al. Filensin is proteolytically processed during lens fibre cell differentiation by multiple independent pathways. Eur J Cell Biol 1995;67:238–53.

    CAS  PubMed  Google Scholar 

  46. 46

    Bilak SR, et al. Properties of the novel intermediate filament protein synemin and its identification in mammalian muscle. Arch Biochem Biophys 1998;355:63–76.

    CAS  PubMed  Google Scholar 

  47. 47

    Granger BL, Lazarides E . Synemin: a new high molecular weight protein associated with desmin and vimentin filaments in muscle. Cell 1980;22:727–38.

    CAS  PubMed  Google Scholar 

  48. 48

    Granger BL, Lazarides E . Expression of the intermediate-filament-associated protein synemin in chicken lens cells. Mol Cell Biol 1984;4:1943–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49

    Colucci-Guyon E, et al. Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 1994;79:679–94.

    CAS  PubMed  Google Scholar 

  50. 50

    Hatfield JS, Skoff RP, Maisel H, Eng L, Bigner DD . The lens epithelium contains glial fibrillary acidic protein (GFAP). J Neuroimmunol 1985;8:347–57.

    CAS  PubMed  Google Scholar 

  51. 51

    Verderber L, Johnson W, Mucke L, Sarthy V . Differential regulation of a glial fibrillary acidic protein-LacZ transgene in retinal astrocytes and Muller cells. Invest Ophthalmol Vis Sci 1995;36:1137–43.

    CAS  PubMed  Google Scholar 

  52. 52

    McLean WH, Lane EB . Intermediate filaments in disease. Curr Opin Cell Biol 1995;7:118–125.

    CAS  PubMed  Google Scholar 

  53. 53

    Steinert PM, Marekov LN, Parry DA . Diversity of intermediate filament structure: evidence that the alignment of coiled-coil molecules in vimentin is different from that in keratin intermediate filaments. J Biol Chem 1993;268:24916–25.

    CAS  PubMed  Google Scholar 

  54. 54

    Ireland M, Maisel H . A cytoskeletal protein unique to lens fibre cell differentiation. Exp Eye Res 1984;38:637–45.

    CAS  PubMed  Google Scholar 

  55. 55

    Ireland M, Maisel H . A family of lens fibre cell specific proteins. Lens Eye Toxic Res 1989;6:623–38.

    CAS  PubMed  Google Scholar 

  56. 56

    FitzGerald PG, Gottlieb W . The Mr 115 kD fibre cell-specific protein is a component of the lens cytoskeleton. Curr Eye Res 1989;8:801–11.

    CAS  PubMed  Google Scholar 

  57. 57

    Truscott RJ, Marcantonio JM, Tomlinson J, Duncan G . Calcium-induced opacification and proteolysis in the intact rat lens. Invest Ophthalmol Vis Sci 1990;31:2405–11.

    CAS  PubMed  Google Scholar 

  58. 58

    Marcantonio JM . Susceptibility of the bovine lens 115 kDa beaded filament protein to degradation by calcium and calpain. Curr Eye Res 1992;11:103–8.

    CAS  PubMed  Google Scholar 

  59. 59

    FitzGerald PG . Age-related changes in a fibre cell specific extrinsic membrane protein. Curr Eye Res 1988;7:1255–62.

    CAS  PubMed  Google Scholar 

  60. 60

    Brunkener M, Georgatos SD . Membrane-binding properties of filensin, a cytoskeletal protein of the lens fibre cells. J Cell Sci 1992;103:709–18.

    CAS  PubMed  Google Scholar 

  61. 61

    Quinlan RA . The soluble plasma membrane-cytoskeleton complexes and aging in the lens. In: Vrensen GFJM, Clauwaert J, eds. Eye lens membranes and aging, vol 15. Leiden: EURAGE, 1991:171–84.

  62. 62

    Inagaki M, et al. Dynamic property of intermediate filaments: regulation by phosphorylation. Bioessays 1996;18:481–7.

    CAS  Google Scholar 

  63. 63

    Ireland ME, Klettner C, Nunlee W . Cyclic AMP-mediated phosphorylation and insolubilisation of a 49-kDa cytoskeletal marker protein of lens fibre terminal differentiation. Exp Eye Res 1993;56:453–61.

    CAS  PubMed  Google Scholar 

  64. 64

    Wiche G, Herrmann H, Leichtfried F, Pytela R . Plectin: a high-molecular-weight cytoskeletal polypeptide component that copurifies with intermediate filaments of the vimentin type. Cold Spring Harbor Symp Quant Biol 1982;46:475–82.

    PubMed  Google Scholar 

  65. 65

    Weitzer G, Wiche G . Plectin from bovine lenses: chemical properties, structural analysis and initial identification of interaction partners. Eur J Biochem 1987;169:41–52.

    CAS  PubMed  Google Scholar 

  66. 66

    Svitkina TM, Verkhovsky AB, Borisy GG . Plectin sidearms mediate interaction of intermediate filaments with microtubules and other components of the cytoskeleton. J Cell Biol 1996;135:991–1007.

    CAS  PubMed  Google Scholar 

  67. 67

    Gurland G, Gundersen GG . Stable, detyrosinated microtubules function to localise vimentin intermediate filaments in fibroblasts. J Cell Biol 1995;131:1275–90.

    CAS  PubMed  Google Scholar 

  68. 68

    Lieska N, Shao D, Kriho V, Yang HY . Expression and distribution of cytoskeletal IFAP-300kD as an index of lens cell differentiation. Curr Eye Res 1991;10:1165–74.

    CAS  PubMed  Google Scholar 

  69. 69

    Skalli O, Jones JC, Gagescu R, Goldman RD . IFAP 300 is common to desmosomes and hemidesmosomes and is a possible linker of intermediate filaments to these junctions. J Cell Biol 1994;125:159–70.

    CAS  PubMed  Google Scholar 

  70. 70

    Millar A, Hooper A, Copeland L, Cummings F, Prescott A . Reorganisation of the microtubule cytoskeleton and centrosomal loss during lens fibre cell differentiation. Nova Acta Leopoldiana 1997, 299:169–83.

    Google Scholar 

  71. 71

    Lo WK, Shaw AP, Wen XJ . Actin filament bundles in cortical fibre cells of the rat lens. Exp Eye Res 1997;65:691–701.

    CAS  PubMed  Google Scholar 

  72. 72

    Aster JC, Brewer GJ, Hanash SM, Maisel H . Band 4.1-like proteins of the bovine lens: effects of differentiation, distribution and extraction characteristics. Biochem J 1984;224:609–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Aster JC, Brewer GJ, Maisel H . The 4.1-like proteins of the bovine lens: spectrin-binding proteins closely related in structure to red blood cell protein 4.1. J Cell Biol 1986;103:115–22.

    CAS  PubMed  Google Scholar 

  74. 74

    Allen DP, Low PS, Dola A, Maisel H . Band 3 and ankyrin homologues are present in eye lens: evidence for all major erythrocyte membrane components in same non-erythroid cell. Biochem Biophys Res Commun 1987;149:266–75.

    CAS  PubMed  Google Scholar 

  75. 75

    Claudio JO, Veneziale RW, Menko AS, Rouleau GA . Expression of schwannomin in lens and Schwann cells. Neuroreport 1997;8:2025–30.

    CAS  PubMed  Google Scholar 

  76. 76

    Woo MK, Fowler VM . Identification and characterisation of tropomodulin and tropomyosin in the adult rat lens. J Cell Sci 1994;107:1359–67.

    CAS  PubMed  Google Scholar 

  77. 77

    Georgatos SD, Weaver DC, Marchesi VT . Site specificity in vimentin-membrane interactions: intermediate filaments subunits associate with the plasma membrane via their head domains. J Cell Biol 1985;100:1962–7.

    CAS  PubMed  Google Scholar 

  78. 78

    Franke WW, Kapprell HP, Cowin P . Plakoglobin is a component of the filamentous subplasmalemmal coat of lens cells. Eur J Cell Biol 1987;43:301–15.

    CAS  PubMed  Google Scholar 

  79. 79

    Heid HW, et al. Cell type-specific desmosomal plaque proteins of the plakoglobin family: plakophilin 1 (band 6 protein). Differentiation 1994;58:113–31.

    CAS  PubMed  Google Scholar 

  80. 80

    Watanabe M, Kobayashi H, Yao R, Maisel H . Adhesion and junction molecules in embryonic and adult lens cell differentiation. Acta Ophthalmol Suppl 1992;205:46–52.

    Google Scholar 

  81. 81

    Graham C, Wistow G . The predominant cadherin in fetal human lens is identical to N-cadherin and is not a candidate locus for the Marner cataract [letter]. Exp Eye Res 1994;59:373–6.

    CAS  PubMed  Google Scholar 

  82. 82

    Horwitz J . Alpha-crystallin can function as a molecular chaperone. Proc Natl Acad Sci USA 1992;89:10449–53.

    CAS  PubMed  Google Scholar 

  83. 83

    Brady JP, et al. Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin. Proc Natl Acad Sci USA 1997;94:884–9.

    CAS  PubMed  Google Scholar 

  84. 84

    Hess JF, Casselman JT, Fitzgerald PG . Chromosomal locations of the genes for the beaded filament proteins cp-115 and cp-47. Curr Eye Res 1995;14:11–8.

    CAS  PubMed  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to R A Quinlan.

Additional information

R.A.Q. and J.M.C. acknowledge the financial support of the Wellcome Trust. J.E.P. and R.D. are supported by MRC and BBSRC-CASE studentships respectively. The support of Pharmacia-Upjohn as the industrial sponsor of the BBSRC-CASE studentship is acknowledged. C.G. is supported by a Fight for Sight studentship

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Quinlan, R., Sandilands, A., Procter, J. et al. The eye lens cytoskeleton. Eye 13, 409–416 (1999). https://doi.org/10.1038/eye.1999.115

Download citation

Keywords

  • CP49
  • Cytoskeleton
  • Differentiation
  • Filensin
  • Intermediate filaments
  • Lens

Further reading

Search