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. 1994 May 1;125(3):511–516. doi: 10.1083/jcb.125.3.511

Intermediate filaments and disease: mutations that cripple cell strength

PMCID: PMC2119985  PMID: 7513705

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Selected References

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  1. Aebi U., Cohn J., Buhle L., Gerace L. The nuclear lamina is a meshwork of intermediate-type filaments. Nature. 1986 Oct 9;323(6088):560–564. doi: 10.1038/323560a0. [DOI] [PubMed] [Google Scholar]
  2. Aebi U., Fowler W. E., Rew P., Sun T. T. The fibrillar substructure of keratin filaments unraveled. J Cell Biol. 1983 Oct;97(4):1131–1143. doi: 10.1083/jcb.97.4.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albers K., Fuchs E. The expression of mutant epidermal keratin cDNAs transfected in simple epithelial and squamous cell carcinoma lines. J Cell Biol. 1987 Aug;105(2):791–806. doi: 10.1083/jcb.105.2.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anton-Lamprecht I. Genetically induced abnormalities of epidermal differentiation and ultrastructure in ichthyoses and epidermolyses: pathogenesis, heterogeneity, fetal manifestation, and prenatal diagnosis. J Invest Dermatol. 1983 Jul;81(1 Suppl):149s–156s. doi: 10.1111/1523-1747.ep12540961. [DOI] [PubMed] [Google Scholar]
  5. Baribault H., Oshima R. G. Polarized and functional epithelia can form after the targeted inactivation of both mouse keratin 8 alleles. J Cell Biol. 1991 Dec;115(6):1675–1684. doi: 10.1083/jcb.115.6.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Baribault H., Price J., Miyai K., Oshima R. G. Mid-gestational lethality in mice lacking keratin 8. Genes Dev. 1993 Jul;7(7A):1191–1202. doi: 10.1101/gad.7.7a.1191. [DOI] [PubMed] [Google Scholar]
  7. Behrendt H. Effect of anabolic steroids on rat heart muscle cells. I. Intermediate filaments. Cell Tissue Res. 1977 May 31;180(3):303–315. doi: 10.1007/BF00227598. [DOI] [PubMed] [Google Scholar]
  8. Bonifas J. M., Rothman A. L., Epstein E. H., Jr Epidermolysis bullosa simplex: evidence in two families for keratin gene abnormalities. Science. 1991 Nov 22;254(5035):1202–1205. doi: 10.1126/science.1720261. [DOI] [PubMed] [Google Scholar]
  9. Chan Y. M., Yu Q. C., Fine J. D., Fuchs E. The genetic basis of Weber-Cockayne epidermolysis bullosa simplex. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7414–7418. doi: 10.1073/pnas.90.15.7414. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chan Y. M., Yu Q. C., LeBlanc-Straceski J., Christiano A., Pulkkinen L., Kucherlapati R. S., Uitto J., Fuchs E. Mutations in the non-helical linker segment L1-2 of keratin 5 in patients with Weber-Cockayne epidermolysis bullosa simplex. J Cell Sci. 1994 Apr;107(Pt 4):765–774. doi: 10.1242/jcs.107.4.765. [DOI] [PubMed] [Google Scholar]
  11. Chen M. A., Bonifas J. M., Matsumura K., Blumenfeld A., Epstein E. H., Jr A novel three-nucleotide deletion in the helix 2B region of keratin 14 in epidermolysis bullosa simplex: delta E375. Hum Mol Genet. 1993 Nov;2(11):1971–1972. doi: 10.1093/hmg/2.11.1971. [DOI] [PubMed] [Google Scholar]
  12. Cheng J., Syder A. J., Yu Q. C., Letai A., Paller A. S., Fuchs E. The genetic basis of epidermolytic hyperkeratosis: a disorder of differentiation-specific epidermal keratin genes. Cell. 1992 Sep 4;70(5):811–819. doi: 10.1016/0092-8674(92)90314-3. [DOI] [PubMed] [Google Scholar]
  13. Chipev C. C., Korge B. P., Markova N., Bale S. J., DiGiovanna J. J., Compton J. G., Steinert P. M. A leucine----proline mutation in the H1 subdomain of keratin 1 causes epidermolytic hyperkeratosis. Cell. 1992 Sep 4;70(5):821–828. doi: 10.1016/0092-8674(92)90315-4. [DOI] [PubMed] [Google Scholar]
  14. Chipev C. C., Yang J. M., DiGiovanna J. J., Steinert P. M., Marekov L., Compton J. G., Bale S. J. Preferential sites in keratin 10 that are mutated in epidermolytic hyperkeratosis. Am J Hum Genet. 1994 Feb;54(2):179–190. [PMC free article] [PubMed] [Google Scholar]
  15. Compton J. G., DiGiovanna J. J., Santucci S. K., Kearns K. S., Amos C. I., Abangan D. L., Korge B. P., McBride O. W., Steinert P. M., Bale S. J. Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q. Nat Genet. 1992 Jul;1(4):301–305. doi: 10.1038/ng0792-301. [DOI] [PubMed] [Google Scholar]
  16. Cooper D. N., Youssoufian H. The CpG dinucleotide and human genetic disease. Hum Genet. 1988 Feb;78(2):151–155. doi: 10.1007/BF00278187. [DOI] [PubMed] [Google Scholar]
  17. Coulombe P. A., Chan Y. M., Albers K., Fuchs E. Deletions in epidermal keratins leading to alterations in filament organization in vivo and in intermediate filament assembly in vitro. J Cell Biol. 1990 Dec;111(6 Pt 2):3049–3064. doi: 10.1083/jcb.111.6.3049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Coulombe P. A., Hutton M. E., Letai A., Hebert A., Paller A. S., Fuchs E. Point mutations in human keratin 14 genes of epidermolysis bullosa simplex patients: genetic and functional analyses. Cell. 1991 Sep 20;66(6):1301–1311. doi: 10.1016/0092-8674(91)90051-y. [DOI] [PubMed] [Google Scholar]
  19. Coulombe P. A., Hutton M. E., Vassar R., Fuchs E. A function for keratins and a common thread among different types of epidermolysis bullosa simplex diseases. J Cell Biol. 1991 Dec;115(6):1661–1674. doi: 10.1083/jcb.115.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Côté F., Collard J. F., Julien J. P. Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell. 1993 Apr 9;73(1):35–46. doi: 10.1016/0092-8674(93)90158-m. [DOI] [PubMed] [Google Scholar]
  21. Dong W., Ryynänen M., Uitto J. Identification of a leucine-to-proline mutation in the keratin 5 gene in a family with the generalized Köbner type of epidermolysis bullosa simplex. Hum Mutat. 1993;2(2):94–102. doi: 10.1002/humu.1380020206. [DOI] [PubMed] [Google Scholar]
  22. Fuchs E., Esteves R. A., Coulombe P. A. Transgenic mice expressing a mutant keratin 10 gene reveal the likely genetic basis for epidermolytic hyperkeratosis. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6906–6910. doi: 10.1073/pnas.89.15.6906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Fuchs E., Weber K. Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem. 1994;63:345–382. doi: 10.1146/annurev.bi.63.070194.002021. [DOI] [PubMed] [Google Scholar]
  24. Geisler N., Schünemann J., Weber K. Chemical cross-linking indicates a staggered and antiparallel protofilament of desmin intermediate filaments and characterizes one higher-level complex between protofilaments. Eur J Biochem. 1992 Jun 15;206(3):841–852. doi: 10.1111/j.1432-1033.1992.tb16992.x. [DOI] [PubMed] [Google Scholar]
  25. Gill S. R., Wong P. C., Monteiro M. J., Cleveland D. W. Assembly properties of dominant and recessive mutations in the small mouse neurofilament (NF-L) subunit. J Cell Biol. 1990 Nov;111(5 Pt 1):2005–2019. doi: 10.1083/jcb.111.5.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hanukoglu I., Fuchs E. The cDNA sequence of a Type II cytoskeletal keratin reveals constant and variable structural domains among keratins. Cell. 1983 Jul;33(3):915–924. doi: 10.1016/0092-8674(83)90034-x. [DOI] [PubMed] [Google Scholar]
  27. Hatzfeld M., Weber K. Modulation of keratin intermediate filament assembly by single amino acid exchanges in the consensus sequence at the C-terminal end of the rod domain. J Cell Sci. 1991 Jun;99(Pt 2):351–362. doi: 10.1242/jcs.99.2.351. [DOI] [PubMed] [Google Scholar]
  28. Heald R., McKeon F. Mutations of phosphorylation sites in lamin A that prevent nuclear lamina disassembly in mitosis. Cell. 1990 May 18;61(4):579–589. doi: 10.1016/0092-8674(90)90470-y. [DOI] [PubMed] [Google Scholar]
  29. Heins S., Wong P. C., Müller S., Goldie K., Cleveland D. W., Aebi U. The rod domain of NF-L determines neurofilament architecture, whereas the end domains specify filament assembly and network formation. J Cell Biol. 1993 Dec;123(6 Pt 1):1517–1533. doi: 10.1083/jcb.123.6.1517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Heitlinger E., Peter M., Häner M., Lustig A., Aebi U., Nigg E. A. Expression of chicken lamin B2 in Escherichia coli: characterization of its structure, assembly, and molecular interactions. J Cell Biol. 1991 May;113(3):485–495. doi: 10.1083/jcb.113.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hisanaga S., Kusubata M., Okumura E., Kishimoto T. Phosphorylation of neurofilament H subunit at the tail domain by CDC2 kinase dissociates the association to microtubules. J Biol Chem. 1991 Nov 15;266(32):21798–21803. [PubMed] [Google Scholar]
  32. Hovnanian A., Pollack E., Hilal L., Rochat A., Prost C., Barrandon Y., Goossens M. A missense mutation in the rod domain of keratin 14 associated with recessive epidermolysis bullosa simplex. Nat Genet. 1993 Apr;3(4):327–332. doi: 10.1038/ng0493-327. [DOI] [PubMed] [Google Scholar]
  33. Humphries M. M., Sheils D. M., Farrar G. J., Kumar-Singh R., Kenna P. F., Mansergh F. C., Jordan S. A., Young M., Humphries P. A mutation (Met-->Arg) in the type I keratin (K14) gene responsible for autosomal dominant epidermolysis bullosa simplex. Hum Mutat. 1993;2(1):37–42. doi: 10.1002/humu.1380020107. [DOI] [PubMed] [Google Scholar]
  34. Janmey P. A., Euteneuer U., Traub P., Schliwa M. Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J Cell Biol. 1991 Apr;113(1):155–160. doi: 10.1083/jcb.113.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kaufmann E., Weber K., Geisler N. Intermediate filament forming ability of desmin derivatives lacking either the amino-terminal 67 or the carboxy-terminal 27 residues. J Mol Biol. 1985 Oct 20;185(4):733–742. doi: 10.1016/0022-2836(85)90058-0. [DOI] [PubMed] [Google Scholar]
  36. Kitajima Y., Inoue S., Yaoita H. Abnormal organization of keratin intermediate filaments in cultured keratinocytes of epidermolysis bullosa simplex. Arch Dermatol Res. 1989;281(1):5–10. doi: 10.1007/BF00424265. [DOI] [PubMed] [Google Scholar]
  37. Klymkowsky M. W., Shook D. R., Maynell L. A. Evidence that the deep keratin filament systems of the Xenopus embryo act to ensure normal gastrulation. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8736–8740. doi: 10.1073/pnas.89.18.8736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Kouklis P. D., Papamarcaki T., Merdes A., Georgatos S. D. A potential role for the COOH-terminal domain in the lateral packing of type III intermediate filaments. J Cell Biol. 1991 Aug;114(4):773–786. doi: 10.1083/jcb.114.4.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lane E. B., Rugg E. L., Navsaria H., Leigh I. M., Heagerty A. H., Ishida-Yamamoto A., Eady R. A. A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering. Nature. 1992 Mar 19;356(6366):244–246. doi: 10.1038/356244a0. [DOI] [PubMed] [Google Scholar]
  40. Letai A., Coulombe P. A., Fuchs E. Do the ends justify the mean? Proline mutations at the ends of the keratin coiled-coil rod segment are more disruptive than internal mutations. J Cell Biol. 1992 Mar;116(5):1181–1195. doi: 10.1083/jcb.116.5.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Letai A., Coulombe P. A., McCormick M. B., Yu Q. C., Hutton E., Fuchs E. Disease severity correlates with position of keratin point mutations in patients with epidermolysis bullosa simplex. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3197–3201. doi: 10.1073/pnas.90.8.3197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Lu X., Lane E. B. Retrovirus-mediated transgenic keratin expression in cultured fibroblasts: specific domain functions in keratin stabilization and filament formation. Cell. 1990 Aug 24;62(4):681–696. doi: 10.1016/0092-8674(90)90114-t. [DOI] [PubMed] [Google Scholar]
  43. McLean W. H., Eady R. A., Dopping-Hepenstal P. J., McMillan J. R., Leigh I. M., Navsaria H. A., Higgins C., Harper J. I., Paige D. G., Morley S. M. Mutations in the rod 1A domain of keratins 1 and 10 in bullous congenital ichthyosiform erythroderma (BCIE). J Invest Dermatol. 1994 Jan;102(1):24–30. doi: 10.1111/1523-1747.ep12371726. [DOI] [PubMed] [Google Scholar]
  44. Nadeau J. H., Berger F. G., Cox D. R., Crosby J. L., Davisson M. T., Ferrara D., Fuchs E., Hart C., Hunihan L., Lalley P. A. A family of type I keratin genes and the homeobox-2 gene complex are closely linked to the rex locus on mouse chromosome 11. Genomics. 1989 Oct;5(3):454–462. doi: 10.1016/0888-7543(89)90009-8. [DOI] [PubMed] [Google Scholar]
  45. Newport J. W., Wilson K. L., Dunphy W. G. A lamin-independent pathway for nuclear envelope assembly. J Cell Biol. 1990 Dec;111(6 Pt 1):2247–2259. doi: 10.1083/jcb.111.6.2247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Nigg E. A. Assembly-disassembly of the nuclear lamina. Curr Opin Cell Biol. 1992 Feb;4(1):105–109. doi: 10.1016/0955-0674(92)90066-l. [DOI] [PubMed] [Google Scholar]
  47. Ohara O., Gahara Y., Miyake T., Teraoka H., Kitamura T. Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J Cell Biol. 1993 Apr;121(2):387–395. doi: 10.1083/jcb.121.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Pellissier J. F., Pouget J., Charpin C., Figarella D. Myopathy associated with desmin type intermediate filaments. An immunoelectron microscopic study. J Neurol Sci. 1989 Jan;89(1):49–61. doi: 10.1016/0022-510x(89)90006-3. [DOI] [PubMed] [Google Scholar]
  49. Powell B. C., Rogers G. E. Cyclic hair-loss and regrowth in transgenic mice overexpressing an intermediate filament gene. EMBO J. 1990 May;9(5):1485–1493. doi: 10.1002/j.1460-2075.1990.tb08266.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Raats J. M., Henderik J. B., Verdijk M., van Oort F. L., Gerards W. L., Ramaekers F. C., Bloemendal H. Assembly of carboxy-terminally deleted desmin in vimentin-free cells. Eur J Cell Biol. 1991 Oct;56(1):84–103. [PubMed] [Google Scholar]
  51. Reis A., Hennies H. C., Langbein L., Digweed M., Mischke D., Drechsler M., Schröck E., Royer-Pokora B., Franke W. W., Sperling K. Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK). Nat Genet. 1994 Feb;6(2):174–179. doi: 10.1038/ng0294-174. [DOI] [PubMed] [Google Scholar]
  52. Rosenberg M., Fuchs E., Le Beau M. M., Eddy R. L., Shows T. B. Three epidermal and one simple epithelial type II keratin genes map to human chromosome 12. Cytogenet Cell Genet. 1991;57(1):33–38. doi: 10.1159/000133109. [DOI] [PubMed] [Google Scholar]
  53. Rothnagel J. A., Dominey A. M., Dempsey L. D., Longley M. A., Greenhalgh D. A., Gagne T. A., Huber M., Frenk E., Hohl D., Roop D. R. Mutations in the rod domains of keratins 1 and 10 in epidermolytic hyperkeratosis. Science. 1992 Aug 21;257(5073):1128–1130. doi: 10.1126/science.257.5073.1128. [DOI] [PubMed] [Google Scholar]
  54. Rugg E. L., Morley S. M., Smith F. J., Boxer M., Tidman M. J., Navsaria H., Leigh I. M., Lane E. B. Missing links: Weber-Cockayne keratin mutations implicate the L12 linker domain in effective cytoskeleton function. Nat Genet. 1993 Nov;5(3):294–300. doi: 10.1038/ng1193-294. [DOI] [PubMed] [Google Scholar]
  55. Steinert P. M., Marekov L. N., Fraser R. D., Parry D. A. Keratin intermediate filament structure. Crosslinking studies yield quantitative information on molecular dimensions and mechanism of assembly. J Mol Biol. 1993 Mar 20;230(2):436–452. doi: 10.1006/jmbi.1993.1161. [DOI] [PubMed] [Google Scholar]
  56. Steinert P. M., Parry D. A. The conserved H1 domain of the type II keratin 1 chain plays an essential role in the alignment of nearest neighbor molecules in mouse and human keratin 1/keratin 10 intermediate filaments at the two- to four-molecule level of structure. J Biol Chem. 1993 Feb 5;268(4):2878–2887. [PubMed] [Google Scholar]
  57. Stephens K., Sybert V. P., Wijsman E. M., Ehrlich P., Spencer A. A keratin 14 mutational hot spot for epidermolysis bullosa simplex, Dowling-Meara: implications for diagnosis. J Invest Dermatol. 1993 Aug;101(2):240–243. doi: 10.1111/1523-1747.ep12365079. [DOI] [PubMed] [Google Scholar]
  58. Stewart M. Intermediate filament structure and assembly. Curr Opin Cell Biol. 1993 Feb;5(1):3–11. doi: 10.1016/s0955-0674(05)80002-x. [DOI] [PubMed] [Google Scholar]
  59. Syder A. J., Yu Q. C., Paller A. S., Giudice G., Pearson R., Fuchs E. Genetic mutations in the K1 and K10 genes of patients with epidermolytic hyperkeratosis. Correlation between location and disease severity. J Clin Invest. 1994 Apr;93(4):1533–1542. doi: 10.1172/JCI117132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Tanigawa G., Jarcho J. A., Kass S., Solomon S. D., Vosberg H. P., Seidman J. G., Seidman C. E. A molecular basis for familial hypertrophic cardiomyopathy: an alpha/beta cardiac myosin heavy chain hybrid gene. Cell. 1990 Sep 7;62(5):991–998. doi: 10.1016/0092-8674(90)90273-h. [DOI] [PubMed] [Google Scholar]
  61. Torchard D., Blanchet-Bardon C., Serova O., Langbein L., Narod S., Janin N., Goguel A. F., Bernheim A., Franke W. W., Lenoir G. M. Epidermolytic palmoplantar keratoderma cosegregates with a keratin 9 mutation in a pedigree with breast and ovarian cancer. Nat Genet. 1994 Jan;6(1):106–110. doi: 10.1038/ng0194-106. [DOI] [PubMed] [Google Scholar]
  62. Torpey N., Wylie C. C., Heasman J. Function of maternal cytokeratin in Xenopus development. Nature. 1992 Jun 4;357(6377):413–415. doi: 10.1038/357413a0. [DOI] [PubMed] [Google Scholar]
  63. Vassar R., Coulombe P. A., Degenstein L., Albers K., Fuchs E. Mutant keratin expression in transgenic mice causes marked abnormalities resembling a human genetic skin disease. Cell. 1991 Jan 25;64(2):365–380. doi: 10.1016/0092-8674(91)90645-f. [DOI] [PubMed] [Google Scholar]
  64. Wiley C. A., Love S., Skoglund R. R., Lampert P. W. Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments. Acta Neuropathol. 1987;72(4):369–376. doi: 10.1007/BF00687269. [DOI] [PubMed] [Google Scholar]
  65. Wilson A. K., Coulombe P. A., Fuchs E. The roles of K5 and K14 head, tail, and R/K L L E G E domains in keratin filament assembly in vitro. J Cell Biol. 1992 Oct;119(2):401–414. doi: 10.1083/jcb.119.2.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wong P. C., Cleveland D. W. Characterization of dominant and recessive assembly-defective mutations in mouse neurofilament NF-M. J Cell Biol. 1990 Nov;111(5 Pt 1):1987–2003. doi: 10.1083/jcb.111.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Xu Z., Cork L. C., Griffin J. W., Cleveland D. W. Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell. 1993 Apr 9;73(1):23–33. doi: 10.1016/0092-8674(93)90157-l. [DOI] [PubMed] [Google Scholar]
  68. Yang J. M., Chipev C. C., DiGiovanna J. J., Bale S. J., Marekov L. N., Steinert P. M., Compton J. G. Mutations in the H1 and 1A domains in the keratin 1 gene in epidermolytic hyperkeratosis. J Invest Dermatol. 1994 Jan;102(1):17–23. doi: 10.1111/1523-1747.ep12371725. [DOI] [PubMed] [Google Scholar]
  69. de Waegh S. M., Lee V. M., Brady S. T. Local modulation of neurofilament phosphorylation, axonal caliber, and slow axonal transport by myelinating Schwann cells. Cell. 1992 Feb 7;68(3):451–463. doi: 10.1016/0092-8674(92)90183-d. [DOI] [PubMed] [Google Scholar]

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