Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Jul;86(1):279–285. doi: 10.1172/JCI114696

The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore.

J C Courvalin 1, K Lassoued 1, E Bartnik 1, G Blobel 1, R W Wozniak 1
PMCID: PMC296718  PMID: 2195063

Abstract

We have recently reported a new family of nuclear autoantibodies in a subset of patients with primary biliary cirrhosis. These antibodies bind to a nuclear envelope polypeptide(s) of approximately 200 kD, the exact identity of which was not established. In this study, we show that all of these autoantibodies are directed against a 210-kD integral membrane glycoprotein of the nuclear pore.

Full text

PDF
279

Images in this article

280Image
on p.280
280Image
on p.280
280Image
on p.280
281Image
on p.281
281Image
on p.281
281Image
on p.281
281Image
on p.281
282Image
on p.282
282Image
on p.282
282Image
on p.282
282Image
on p.282
282Image
on p.282
283Image
on p.283
283Image
on p.283
283Image
on p.283
283Image
on p.283

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berg P. A., Klein R. Immunology of primary biliary cirrhosis. Baillieres Clin Gastroenterol. 1987 Jul;1(3):675–706. doi: 10.1016/0950-3528(87)90053-4. [DOI] [PubMed] [Google Scholar]
  2. Bernstein R. M., Callender M. E., Neuberger J. M., Hughes G. R., Williams R. Anticentromere antibody in primary biliary cirrhosis. Ann Rheum Dis. 1982 Dec;41(6):612–614. doi: 10.1136/ard.41.6.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernstein R. M., Neuberger J. M., Bunn C. C., Callender M. E., Hughes G. R., Williams R. Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis. Clin Exp Immunol. 1984 Mar;55(3):553–560. [PMC free article] [PubMed] [Google Scholar]
  4. Berrios M., Blobel G., Fisher P. A. Characterization of an ATPase/dATPase activity associated with the Drosophila nuclear matrix-pore complex-lamina fraction. Identification of the putative enzyme polypeptide by direct ultraviolet photoaffinity labeling. J Biol Chem. 1983 Apr 10;258(7):4548–4555. [PubMed] [Google Scholar]
  5. Berrios M., Filson A. J., Blobel G., Fisher P. A. A 174-kilodalton ATPase/dATPase polypeptide and a glycoprotein of apparently identical molecular weight are common but distinct components of higher eukaryotic nuclear structural protein subfractions. J Biol Chem. 1983 Nov 10;258(21):13384–13390. [PubMed] [Google Scholar]
  6. Blobel G., Potter V. R. Nuclei from rat liver: isolation method that combines purity with high yield. Science. 1966 Dec 30;154(3757):1662–1665. doi: 10.1126/science.154.3757.1662. [DOI] [PubMed] [Google Scholar]
  7. Bonner W. M., Laskey R. A. A film detection method for tritium-labelled proteins and nucleic acids in polyacrylamide gels. Eur J Biochem. 1974 Jul 1;46(1):83–88. doi: 10.1111/j.1432-1033.1974.tb03599.x. [DOI] [PubMed] [Google Scholar]
  8. Chambers J. C., Keene J. D. Isolation and analysis of cDNA clones expressing human lupus La antigen. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2115–2119. doi: 10.1073/pnas.82.7.2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Christensen E., Crowe J., Doniach D., Popper H., Ranek L., Rodés J., Tygstrup N., Williams R. Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients. Gastroenterology. 1980 Feb;78(2):236–246. [PubMed] [Google Scholar]
  10. Coppel R. L., McNeilage L. J., Surh C. D., Van de Water J., Spithill T. W., Whittingham S., Gershwin M. E. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7317–7321. doi: 10.1073/pnas.85.19.7317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dagenais A., Bibor-Hardy V., Senécal J. L. A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes. Arthritis Rheum. 1988 Oct;31(10):1322–1327. doi: 10.1002/art.1780311017. [DOI] [PubMed] [Google Scholar]
  12. Davis L. I., Blobel G. Identification and characterization of a nuclear pore complex protein. Cell. 1986 Jun 6;45(5):699–709. doi: 10.1016/0092-8674(86)90784-1. [DOI] [PubMed] [Google Scholar]
  13. Davis L. I., Blobel G. Nuclear pore complex contains a family of glycoproteins that includes p62: glycosylation through a previously unidentified cellular pathway. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7552–7556. doi: 10.1073/pnas.84.21.7552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dingwall C., Laskey R. A. Protein import into the cell nucleus. Annu Rev Cell Biol. 1986;2:367–390. doi: 10.1146/annurev.cb.02.110186.002055. [DOI] [PubMed] [Google Scholar]
  15. Gerace L., Burke B. Functional organization of the nuclear envelope. Annu Rev Cell Biol. 1988;4:335–374. doi: 10.1146/annurev.cb.04.110188.002003. [DOI] [PubMed] [Google Scholar]
  16. Gerace L., Comeau C., Benson M. Organization and modulation of nuclear lamina structure. J Cell Sci Suppl. 1984;1:137–160. doi: 10.1242/jcs.1984.supplement_1.10. [DOI] [PubMed] [Google Scholar]
  17. Gerace L., Ottaviano Y., Kondor-Koch C. Identification of a major polypeptide of the nuclear pore complex. J Cell Biol. 1982 Dec;95(3):826–837. doi: 10.1083/jcb.95.3.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ishii H., Saifuku K., Namihisa T. Reactivities and clinical relevance of antimitochondrial antibodies to four mitochondrial inner membrane proteins in sera of patients with primary biliary cirrhosis. Hepatology. 1987 Jan-Feb;7(1):134–136. doi: 10.1002/hep.1840070126. [DOI] [PubMed] [Google Scholar]
  19. Kaplan M. M. Primary biliary cirrhosis. N Engl J Med. 1987 Feb 26;316(9):521–528. doi: 10.1056/NEJM198702263160907. [DOI] [PubMed] [Google Scholar]
  20. Kaufmann S. H., Gibson W., Shaper J. H. Characterization of the major polypeptides of the rat liver nuclear envelope. J Biol Chem. 1983 Feb 25;258(4):2710–2719. [PubMed] [Google Scholar]
  21. Kurki P., Gripenberg M., Teppo A. M., Salaspuro M. Profiles of antinuclear antibodies in chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease. Liver. 1984 Apr;4(2):134–138. doi: 10.1111/j.1600-0676.1984.tb00918.x. [DOI] [PubMed] [Google Scholar]
  22. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  23. Lassoued K., Guilly M. N., Andre C., Paintrand M., Dhumeaux D., Danon F., Brouet J. C., Courvalin J. C. Autoantibodies to 200 kD polypeptide(s) of the nuclear envelope: a new serologic marker of primary biliary cirrhosis. Clin Exp Immunol. 1988 Nov;74(2):283–288. [PMC free article] [PubMed] [Google Scholar]
  24. Lassoued K., Guilly M. N., Danon F., Andre C., Dhumeaux D., Clauvel J. P., Brouet J. C., Seligmann M., Courvalin J. C. Antinuclear autoantibodies specific for lamins. Characterization and clinical significance. Ann Intern Med. 1988 Jun;108(6):829–833. doi: 10.7326/0003-4819-108-6-829. [DOI] [PubMed] [Google Scholar]
  25. Lieu T. S., Newkirk M. M., Capra J. D., Sontheimer R. D. Molecular characterization of human Ro/SS-A antigen. Amino terminal sequence of the protein moiety of human Ro/SS-A antigen and immunological activity of a corresponding synthetic peptide. J Clin Invest. 1988 Jul;82(1):96–101. doi: 10.1172/JCI113607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lindenborn-Fotinos J., Baum H., Berg P. A. Mitochondrial antibodies in primary biliary cirrhosis: species and nonspecies specific determinants of M2 antigen. Hepatology. 1985 Sep-Oct;5(5):763–769. doi: 10.1002/hep.1840050510. [DOI] [PubMed] [Google Scholar]
  27. Lozano F., Parés A., Borche L., Plana M., Gallart T., Rodés J., Vives J. Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis. Hepatology. 1988 Jul-Aug;8(4):930–938. doi: 10.1002/hep.1840080438. [DOI] [PubMed] [Google Scholar]
  28. Makinen D., Fritzler M., Davis P., Sherlock S. Anticentromere antibodies in primary biliary cirrhosis. Arthritis Rheum. 1983 Jul;26(7):914–917. doi: 10.1002/art.1780260714. [DOI] [PubMed] [Google Scholar]
  29. Melms A., Chrestel S., Schalke B. C., Wekerle H., Mauron A., Ballivet M., Barkas T. Autoimmune T lymphocytes in myasthenia gravis. Determination of target epitopes using T lines and recombinant products of the mouse nicotinic acetylcholine receptor gene. J Clin Invest. 1989 Mar;83(3):785–790. doi: 10.1172/JCI113958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mouritsen S., Demant E., Permin H., Wiik A. High prevalence of anti-mitochondrial antibodies among patients with some well-defined connective tissue diseases. Clin Exp Immunol. 1986 Oct;66(1):68–76. [PMC free article] [PubMed] [Google Scholar]
  31. Munoz L. E., Thomas H. C., Scheuer P. J., Doniach D., Sherlock S. Is mitochondrial antibody diagnostic of primary biliary cirrhosis? Gut. 1981 Feb;22(2):136–140. doi: 10.1136/gut.22.2.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Penner E., Muller S., Zimmermann D., Van Regenmortel M. H. High prevalence of antibodies to histones among patients with primary biliary cirrhosis. Clin Exp Immunol. 1987 Oct;70(1):47–52. [PMC free article] [PubMed] [Google Scholar]
  33. Powell F., Schroeter A. L., Dickson E. R. Antinuclear antibodies in primary biliary cirrhosis. Lancet. 1984 Feb 4;1(8371):288–289. doi: 10.1016/s0140-6736(84)90164-8. [DOI] [PubMed] [Google Scholar]
  34. Ruffatti A., Arslan P., Floreani A., De Silvestro G., Calligaro A., Naccarato R., Todesco S. Nuclear membrane-staining antinuclear antibody in patients with primary biliary cirrhosis. J Clin Immunol. 1985 Sep;5(5):357–361. doi: 10.1007/BF00918255. [DOI] [PubMed] [Google Scholar]
  35. Sherlock S., Scheuer P. J. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med. 1973 Sep 27;289(13):674–678. doi: 10.1056/NEJM197309272891306. [DOI] [PubMed] [Google Scholar]
  36. Snow C. M., Senior A., Gerace L. Monoclonal antibodies identify a group of nuclear pore complex glycoproteins. J Cell Biol. 1987 May;104(5):1143–1156. doi: 10.1083/jcb.104.5.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Surh C. D., Danner D. J., Ahmed A., Coppel R. L., Mackay I. R., Dickson E. R., Gershwin M. E. Reactivity of primary biliary cirrhosis sera with a human fetal liver cDNA clone of branched-chain alpha-keto acid dehydrogenase dihydrolipoamide acyltransferase, the 52 kD mitochondrial autoantigen. Hepatology. 1989 Jan;9(1):63–68. doi: 10.1002/hep.1840090110. [DOI] [PubMed] [Google Scholar]
  38. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  39. Wozniak R. W., Bartnik E., Blobel G. Primary structure analysis of an integral membrane glycoprotein of the nuclear pore. J Cell Biol. 1989 Jun;108(6):2083–2092. doi: 10.1083/jcb.108.6.2083. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES