Archives of Dermatological Research

, Volume 298, Issue 8, pp 389–396 | Cite as

Interactions of human tenascin-X domains with dermal extracellular matrix molecules

  • David EggingEmail author
  • Franka van den Berkmortel
  • Glen Taylor
  • Jim Bristow
  • Joost Schalkwijk
Original Paper


Tenascin-X (TNX) is a large 450 kDa extracellular matrix protein expressed in a variety of tissues including skin, joints and blood vessels. Deficiency of TNX causes a recessive form of Ehlers–Danlos syndrome characterized by joint hypermobility, skin fragility and hyperextensible skin. Skin of TNX deficient patients shows abnormal elastic fibers and reduced collagen deposition. The mechanism by which TNX deficiency leads to connective tissue alterations is unknown. Here we report that C-terminal domains of human TNX bind to major dermal fibrillar collagens and tropoelastin. We have mapped these interactions to the fibronectin type III repeat 29 (FNIII29) and the C-terminal fibrinogen domain (FbgX) of TNX. In addition we found that FNIII29 of TNX accelerates collagen fibrillogenesis in vitro. We hypothesize that TNX contributes to matrix stability and is possibly involved in collagen fibril formation.


Tenascin-X Collagen Elastin Fibrillogenesis Ehlers–Danlos syndrome 



The authors are grateful to Dr P. Handford, Dr N. Grebenchtchikov and Dr R. Mecham for providing biological reagents used in this study.

Supplementary material

403_2006_706_MOESM1_ESM.doc (19 kb)
Supplementary material 1
403_2006_706_MOESM2_ESM.doc (19 kb)
Supplementary material 2
403_2006_706_MOESM3_ESM.doc (19 kb)
Supplementary material 3
403_2006_706_MOESM4_ESM.doc (19 kb)
Supplementary material 4
403_2006_706_MOESM5_ESM.doc (20 kb)
Supplementary material 5
403_2006_706_MOESM6_ESM.doc (19 kb)
Supplementary material 6


  1. 1.
    Bristow J, Tee MK, Gitelman SE, Mellon SH, Miller WL (1993) Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B. J Cell Biol 122:265–278PubMedCrossRefGoogle Scholar
  2. 2.
    Burch GH, Gong Y, Liu W, Dettman RW, Curry CJ, Smith L, Miller WL, Bristow J (1997) Tenascin-X deficiency is associated with Ehlers–Danlos syndrome (see comments). Nat Genet 17:104–108PubMedCrossRefGoogle Scholar
  3. 3.
    Egging DF, van Vlijmen I, Starcher B, Gijsen Y, Zweers MC, Blankevoort L, Bristow J, Schalkwijk J (2006) Dermal connective tissue development in mice: an essential role for tenascin-X. Cell Tissue Res 323:465–474PubMedCrossRefGoogle Scholar
  4. 4.
    Elefteriou F, Exposito J, Garrone R, Lethias C (2001) Binding of tenascin-X to decorin. FEBS Lett 495:44–47PubMedCrossRefGoogle Scholar
  5. 5.
    Elefteriou F, Exposito JY, Garrone R, Lethias C (1997) Characterization of the bovine tenascin-X. J Biol Chem 272:22866–22874PubMedCrossRefGoogle Scholar
  6. 6.
    Ikuta T, Sogawa N, Ariga H, Ikemura T, Matsumoto K (1998) Structural analysis of mouse tenascin-X: evolutionary aspects of reduplication of FNIII repeats in the tenascin gene family. Gene 217:1–13PubMedCrossRefGoogle Scholar
  7. 7.
    Jensen SA, Corbett AR, Knott V, Redfield C, Handford PA (2005) Ca2+ -dependent interface formation in fibrillin-1. J Biol Chem 280:14076–14084PubMedCrossRefGoogle Scholar
  8. 8.
    Kadler KE, Holmes DF, Trotter JA, Chapman JA (1996) Collagen fibril formation. Biochem J 316(Pt1):1–11PubMedGoogle Scholar
  9. 9.
    Kettle S, Yuan X, Grundy G, Knott V, Downing AK, Handford PA (1999) Defective calcium binding to fibrillin-1: consequence of an N2144S change for fibrillin-1 structure and function. J Mol Biol 285:1277–1287PubMedCrossRefGoogle Scholar
  10. 10.
    Kozel BA, Wachi H, Davis EC, Mecham RP (2003) Domains in tropoelastin that mediate elastin deposition in vitro and in vivo. J Biol Chem 278:18491–18498PubMedCrossRefGoogle Scholar
  11. 11.
    Lee SS, Knott V, Jovanovic J, Harlos K, Grimes JM, Choulier L, Mardon HJ, Stuart DI, Handford PA (2004) Structure of the integrin binding fragment from fibrillin-1 gives new insights into microfibril organization. Structure (Camb) 12:717–729CrossRefGoogle Scholar
  12. 12.
    Lethias C, Descollonges Y, Boutillon MM, Garrone R (1996) Flexilin: a new extracellular matrix glycoprotein localized on collagen fibrils. Matrix Biol 15:11–19PubMedCrossRefGoogle Scholar
  13. 13.
    Lethias C, Elefteriou F, Parsiegla G, Exposito JY, Garrone R (2001) Identification and characterization of a conformational heparin-binding site involving two fibronectin type iii modules of bovine tenascin-X. J Biol Chem 276:16432–16438PubMedCrossRefGoogle Scholar
  14. 14.
    Lindor NM, Bristow J (2005) Tenascin-X deficiency in autosomal recessive Ehlers–Danlos syndrome. Am J Med Genet A 135(1):75–80PubMedGoogle Scholar
  15. 15.
    Mao JR, Taylor G, Dean WB, Wagner DR, Afzal V, Lotz JC, Rubin EM, Bristow J (2002) Tenascin-X deficiency mimics Ehlers–Danlos syndrome in mice through alteration of collagen deposition. Nat Genet 30:421–425PubMedCrossRefGoogle Scholar
  16. 16.
    Matsumoto K, Saga Y, Ikemura T, Sakakura T, Chiquet ER (1994) The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C. J Cell Biol 125:483–493PubMedCrossRefGoogle Scholar
  17. 17.
    McGettrick AJ, Knott V, Willis A, Handford PA (2000) Molecular effects of calcium binding mutations in Marfan syndrome depend on domain context. Hum Mol Genet 9:1987–1994PubMedCrossRefGoogle Scholar
  18. 18.
    Minamitani T, Ikuta T, Saito Y, Takebe G, Sato M, Sawa H, Nishimura T, Nakamura F, Takahashi K, Ariga H, Matsumoto K (2004) Modulation of collagen fibrillogenesis by tenascin-X and type VI collagen. Exp Cell Res 298:305–315PubMedCrossRefGoogle Scholar
  19. 19.
    Morel Y, Bristow J, Gitelman SE, Miller WL (1989) Transcript encoded on the opposite strand of the human steroid 21-hydroxylase/complement component C4 gene locus. Proc Natl Acad Sci USA 86:6582–6586PubMedCrossRefGoogle Scholar
  20. 20.
    Peeters ACTM, Kucharekova M, Timmermans J, van den Berkmortel FWPJ, Boers GH, Novakova IRO, Egging D, den Heijer M, Schalkwijk J (2004) A clinical and cardiovascular survey of Ehlers–Danlos syndrome patients with complete deficiency of tenascin-X. Neth J Med 62:23–25Google Scholar
  21. 21.
    Reinhardt DP, Mechling DE, Boswell BA, Keene DR, Sakai LY, Bachinger HP (1997) Calcium determines the shape of fibrillin. J Biol Chem 272:7368–7373PubMedCrossRefGoogle Scholar
  22. 22.
    Schalkwijk J, Zweers MC, Steijlen PM, Dean WB, Taylor G, Van Vlijmen IM, van Haren B, Miller WL, Bristow J (2001) A recessive form of the Ehlers–Danlos syndrome caused by tenascin-X deficiency. N Engl J Med 345:1167–1175PubMedCrossRefGoogle Scholar
  23. 23.
    Tee MK, Thomson AA, Bristow J, Miller WL (1995) Sequences promoting the transcription of the human XA gene overlapping P450c21A correctly predict the presence of a novel, adrenal-specific, truncated form of tenascin-X. Genomics 28:171–178PubMedCrossRefGoogle Scholar
  24. 24.
    Whiteman P, Downing AK, Handford PA (1998) NMR analysis of cbEGF domains gives new insights into the structural consequences of a P1148A substitution in fibrillin-1. Protein Eng 11:957–959PubMedCrossRefGoogle Scholar
  25. 25.
    Whiteman P, Smallridge RS, Knott V, Cordle JJ, Downing AK, Handford PA (2001) A G1127S change in calcium-binding epidermal growth factor-like domain 13 of human fibrillin-1 causes short range conformational effects. J Biol Chem 276:17156–17162PubMedCrossRefGoogle Scholar
  26. 26.
    Williams BR, Gelman RA, Poppke DC, Piez KA (1978) Collagen fibril formation. Optimal in vitro conditions and preliminary kinetic results. J Biol Chem 253:6578–6585PubMedGoogle Scholar
  27. 27.
    Zweers MC, Bristow J, Steijlen PM, Dean WB, Hamel BC, Otero M, Kucharekova M, Boezeman JB, Schalkwijk J (2003) Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers–Danlos syndrome. Am J Hum Genet 73:214–217PubMedCrossRefGoogle Scholar
  28. 28.
    Zweers MC, Vlijmen-Willems IM, Van Kuppevelt TH, Mecham RP, Steijlen PM, Bristow J, Schalkwijk J (2004) Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology. J Invest Dermatol 122:885–891PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • David Egging
    • 1
    Email author
  • Franka van den Berkmortel
    • 1
  • Glen Taylor
    • 2
  • Jim Bristow
    • 2
    • 3
  • Joost Schalkwijk
    • 1
  1. 1.Department of Dermatology, Nijmegen Centre for Molecular Life SciencesRadboud University Nijmegen Medical CentreNijmegenThe Netherlands
  2. 2.Department of PediatricsUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Genome SciencesLawrence Berkeley National LaboratoryBerkeleyUSA

Personalised recommendations