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. 1994 Mar 1;124(5):855–863. doi: 10.1083/jcb.124.5.855

Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices

PMCID: PMC2119952  PMID: 8120105

Abstract

During the previous cloning of the fibrillin gene (FBN1), we isolated a partial cDNA coding for a fibrillin-like peptide and mapped the corresponding gene (FBN2) to human chromosome 5. (Lee, B., M. Godfrey, E. Vitale, H. Hori, M. G. Mattei, M. Sarfarazi, P. Tsipouras, F. Ramirez, and D. W. Hollister. 1991. Nature [Lond.]. 352:330-334). The study left, however, unresolved whether or not the FBN2 gene product is an extracellular component structurally related to fibrillin. Work presented in this report clarifies this important point. Determination of the entire primary structure of the FBN2 gene product demonstrated that this polypeptide is highly homologous to fibrillin. Immunoelectron microscopy localized both fibrillin proteins to elastin-associated extracellular microfibrils. Finally, immunohistochemistry revealed that the fibrillins co-distribute in elastic and non-elastic connective tissues of the developing embryo, with preferential accumulation of the FBN2 gene product in elastic fiber-rich matrices. These results support the original hypothesis that the fibrillins may have distinct but related functions in the formation and maintenance of extracellular microfibrils. Accordingly, we propose to classify the FBN1 and FBN2 gene products as a new family of extracellular proteins and to name its members fibrillin-1 and fibrillin-2, respectively.

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Selected References

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  1. Chen Y., Faraco J., Yin W., Germiller J., Francke U., Bonadio J. Structure, chromosomal localization, and expression pattern of the murine Magp gene. J Biol Chem. 1993 Dec 25;268(36):27381–27389. [PubMed] [Google Scholar]
  2. Claassen L. A., Grossman L. Deletion mutagenesis of the Escherichia coli UvrA protein localizes domains for DNA binding, damage recognition, and protein-protein interactions. J Biol Chem. 1991 Jun 15;266(17):11388–11394. [PubMed] [Google Scholar]
  3. Cleary E. G., Gibson M. A. Elastin-associated microfibrils and microfibrillar proteins. Int Rev Connect Tissue Res. 1983;10:97–209. doi: 10.1016/b978-0-12-363710-9.50009-5. [DOI] [PubMed] [Google Scholar]
  4. Corson G. M., Chalberg S. C., Dietz H. C., Charbonneau N. L., Sakai L. Y. Fibrillin binds calcium and is coded by cDNAs that reveal a multidomain structure and alternatively spliced exons at the 5' end. Genomics. 1993 Aug;17(2):476–484. doi: 10.1006/geno.1993.1350. [DOI] [PubMed] [Google Scholar]
  5. Davis C. G. The many faces of epidermal growth factor repeats. New Biol. 1990 May;2(5):410–419. [PubMed] [Google Scholar]
  6. Dietz H. C., Cutting G. R., Pyeritz R. E., Maslen C. L., Sakai L. Y., Corson G. M., Puffenberger E. G., Hamosh A., Nanthakumar E. J., Curristin S. M. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991 Jul 25;352(6333):337–339. doi: 10.1038/352337a0. [DOI] [PubMed] [Google Scholar]
  7. Dietz H. C., McIntosh I., Sakai L. Y., Corson G. M., Chalberg S. C., Pyeritz R. E., Francomano C. A. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics. 1993 Aug;17(2):468–475. doi: 10.1006/geno.1993.1349. [DOI] [PubMed] [Google Scholar]
  8. Dietz H. C., Pyeritz R. E., Puffenberger E. G., Kendzior R. J., Jr, Corson G. M., Maslen C. L., Sakai L. Y., Francomano C. A., Cutting G. R. Marfan phenotype variability in a family segregating a missense mutation in the epidermal growth factor-like motif of the fibrillin gene. J Clin Invest. 1992 May;89(5):1674–1680. doi: 10.1172/JCI115766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dietz H. C., Saraiva J. M., Pyeritz R. E., Cutting G. R., Francomano C. A. Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. Hum Mutat. 1992;1(5):366–374. doi: 10.1002/humu.1380010504. [DOI] [PubMed] [Google Scholar]
  10. Dietz H. C., Valle D., Francomano C. A., Kendzior R. J., Jr, Pyeritz R. E., Cutting G. R. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. doi: 10.1126/science.8430317. [DOI] [PubMed] [Google Scholar]
  11. Gibson M. A., Kumaratilake J. S., Cleary E. G. The protein components of the 12-nanometer microfibrils of elastic and nonelastic tissues. J Biol Chem. 1989 Mar 15;264(8):4590–4598. [PubMed] [Google Scholar]
  12. Gibson M. A., Sandberg L. B., Grosso L. E., Cleary E. G. Complementary DNA cloning establishes microfibril-associated glycoprotein (MAGP) to be a discrete component of the elastin-associated microfibrils. J Biol Chem. 1991 Apr 25;266(12):7596–7601. [PubMed] [Google Scholar]
  13. Gribskov M., Burgess R. R. Sigma factors from E. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins. Nucleic Acids Res. 1986 Aug 26;14(16):6745–6763. doi: 10.1093/nar/14.16.6745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hendrix M. J., Hay E. D., von der Mark K., Linsenmayer T. F. Immunohistochemical localization of collagen types I and II in the developing chick cornea and tibia by electron microscopy. Invest Ophthalmol Vis Sci. 1982 Mar;22(3):359–375. [PubMed] [Google Scholar]
  15. Hewett D. R., Lynch J. R., Smith R., Sykes B. C. A novel fibrillin mutation in the Marfan syndrome which could disrupt calcium binding of the epidermal growth factor-like module. Hum Mol Genet. 1993 Apr;2(4):475–477. doi: 10.1093/hmg/2.4.475. [DOI] [PubMed] [Google Scholar]
  16. Horrigan S. K., Rich C. B., Streeten B. W., Li Z. Y., Foster J. A. Characterization of an associated microfibril protein through recombinant DNA techniques. J Biol Chem. 1992 May 15;267(14):10087–10095. [PubMed] [Google Scholar]
  17. Kainulainen K., Pulkkinen L., Savolainen A., Kaitila I., Peltonen L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990 Oct 4;323(14):935–939. doi: 10.1056/NEJM199010043231402. [DOI] [PubMed] [Google Scholar]
  18. Kainulainen K., Sakai L. Y., Child A., Pope F. M., Puhakka L., Ryhänen L., Palotie A., Kaitila I., Peltonen L. Two mutations in Marfan syndrome resulting in truncated fibrillin polypeptides. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5917–5921. doi: 10.1073/pnas.89.13.5917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kanzaki T., Olofsson A., Morén A., Wernstedt C., Hellman U., Miyazono K., Claesson-Welsh L., Heldin C. H. TGF-beta 1 binding protein: a component of the large latent complex of TGF-beta 1 with multiple repeat sequences. Cell. 1990 Jun 15;61(6):1051–1061. doi: 10.1016/0092-8674(90)90069-q. [DOI] [PubMed] [Google Scholar]
  20. LOW F. N. Microfibrils: fine filamentous components of the tissue space. Anat Rec. 1962 Feb;142:131–137. doi: 10.1002/ar.1091420205. [DOI] [PubMed] [Google Scholar]
  21. Lee B., D'Alessio M., Ramirez F. Modifications in the organization and expression of collagen genes associated with skeletal disorders. Crit Rev Eukaryot Gene Expr. 1991;1(3):173–187. [PubMed] [Google Scholar]
  22. Lee B., Godfrey M., Vitale E., Hori H., Mattei M. G., Sarfarazi M., Tsipouras P., Ramirez F., Hollister D. W. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991 Jul 25;352(6333):330–334. doi: 10.1038/352330a0. [DOI] [PubMed] [Google Scholar]
  23. Maslen C. L., Corson G. M., Maddox B. K., Glanville R. W., Sakai L. Y. Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991 Jul 25;352(6333):334–337. doi: 10.1038/352334a0. [DOI] [PubMed] [Google Scholar]
  24. Pereira L., D'Alessio M., Ramirez F., Lynch J. R., Sykes B., Pangilinan T., Bonadio J. Genomic organization of the sequence coding for fibrillin, the defective gene product in Marfan syndrome. Hum Mol Genet. 1993 Jul;2(7):961–968. doi: 10.1093/hmg/2.7.961. [DOI] [PubMed] [Google Scholar]
  25. Ramirez F., Pereira L., Zhang H., Lee B. The fibrillin-Marfan syndrome connection. Bioessays. 1993 Sep;15(9):589–594. doi: 10.1002/bies.950150904. [DOI] [PubMed] [Google Scholar]
  26. Sakai L. Y., Keene D. R., Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986 Dec;103(6 Pt 1):2499–2509. doi: 10.1083/jcb.103.6.2499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sakai L. Y., Keene D. R., Glanville R. W., Bächinger H. P. Purification and partial characterization of fibrillin, a cysteine-rich structural component of connective tissue microfibrils. J Biol Chem. 1991 Aug 5;266(22):14763–14770. [PubMed] [Google Scholar]
  28. Tsipouras P., Del Mastro R., Sarfarazi M., Lee B., Vitale E., Child A. H., Godfrey M., Devereux R. B., Hewett D., Steinmann B. Genetic linkage of the Marfan syndrome, ectopia lentis, and congenital contractural arachnodactyly to the fibrillin genes on chromosomes 15 and 5. The International Marfan Syndrome Collaborative Study. N Engl J Med. 1992 Apr 2;326(14):905–909. doi: 10.1056/NEJM199204023261401. [DOI] [PubMed] [Google Scholar]
  29. von der Mark K., von der Mark H., Timpl R., Trelstad R. L. Immunofluorescent localization of collagen types I, II, and III in the embryonic chick eye. Dev Biol. 1977 Aug;59(1):75–85. doi: 10.1016/0012-1606(77)90241-x. [DOI] [PubMed] [Google Scholar]

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