Skip to main content
SpringerLink
Log in

Hyaluronan: Genetic insights into the complex biology of a simple polysaccharide

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

It is appropriate that this review should appear in a volume dedicated to Mert Bernfield. Much of my interest in the cell biology of the extracellular matrix, particularly during development, echoes Mert's pioneering studies. His kind but provocative questioning during meetings is especially missed. The glycosaminoglycan hyaluronan is ubiquitous, and is especially abundant during embryogenesis. Hydrated matrices rich in hyaluronan expand the extracellular space, facilitating cell migration. The viscoelastic properties of hyaluronan are also essential for proper function of cartilage and joints. Recent understanding of hyaluronan biology has benefited from the identification of genes encoding hyaluronan synthases and hyaluronidases, genetic analysis of the roles of hyaluronan during development, elucidation of the biochemical mechanisms of hyaluronan synthesis, and by studies of human genetics and tumors. This review focuses on recent studies utilizing hyaluronan-deficient, gene targeted mice with null alleles for the principal source of hyaluronan during mid-gestation, hyaluronan synthase-2 (has-2). Published in 2003.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Shyjan AM, Heldin P, Butcher EC, Yoshino T, Briskin MJ, Functional cloning of the cDNA for a human hyaluronan synthase, J Biol Chem 271(38), 23395–9 (1996).

    PubMed  Google Scholar 

  2. Itano N, Kimata K, Molecular cloning of human hyaluronan synthase, Biochem Biophys Res Commun 222(3), 816–20 (1996).

    PubMed  Google Scholar 

  3. Watanabe K, Yamaguchi Y, Molecular identification of a putative human hyaluronan synthase, J Biol Chem 271(38), 22945–8 (1996).

    PubMed  Google Scholar 

  4. Spicer AP, Augustine ML, McDonald JA, Molecular cloning and characterization of a putative mouse hyaluronan synthase, J Biol Chem 271(38), 23400–6 (1996).

    PubMed  Google Scholar 

  5. Spicer AP, Olson JS, McDonald JA, Molecular cloning and characterization of a cDNA encoding the third putative mammalian hyaluronan synthase, J Biol Chem 272(14), 8957–61 (1997).

    PubMed  Google Scholar 

  6. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, et al., Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties, J Biol Chem 274(35), 25085–92 (1999).

    PubMed  Google Scholar 

  7. Spicer AP, McDonald JA, Characterization and molecular evolution of a vertebrate hyaluronan synthase gene family, J Biol Chem 273(4), 1923–32 (1998).

    PubMed  Google Scholar 

  8. Yoshida M, Itano N, Yamada Y, Kimata K, in vitro synthesis of hyaluronan by a single protein derived from mouse HAS-1 gene and characterization of amino acid residues essential for the activity, J Biol Chem 275(1), 497–506 (2000).

    PubMed  Google Scholar 

  9. Pummill PE, Kempner ES, DeAngelis PL, Functional molecular mass of a vertebrate hyaluronan synthase as determined by radiation inactivation analysis, J Biol Chem 276(43), 39832–5 (2001).

    PubMed  Google Scholar 

  10. Spicer AP, Seldin MF, Olsen AS, Brown N, Wells DE, Doggett NA, et al., Chromosomal localization of the human and mouse hyaluronan synthase genes, Genomics 41(3), 493–7 (1997).

    PubMed  Google Scholar 

  11. Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A Jr, et al., Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme, J Clin Invest 106(3), 349–60 (2000).

    PubMed  Google Scholar 

  12. Mjaatvedt CH, Yamamura H, Capehart AA, Turner D, Markwald RR, The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation, Dev Biol 202(1), 56–66 (1998).

    PubMed  Google Scholar 

  13. Yamamura H, Zhang M, Markwald RR, Mjaatvedt CH, A heart segmental defect in the anterior-posterior axis of a transgenic mutant mouse, Dev Biol 186(1), 58–72 (1997).

    PubMed  Google Scholar 

  14. Zhuo L, Yoneda M, Zhao M, Yingsung W, Yoshida N, Kitagawa Y, et al., Defect in SHAP-hyaluronan complex causes severe female infertility. A study by inactivation of the bikunin gene in mice, J Biol Chem 276(11), 7693-6 (2001).

    PubMed  Google Scholar 

  15. Day AJ, Prestwich GD, Hyaluronan-binding proteins: Tying up the giant, J Biol Chem 277(7), 4585-8 (2002).

    PubMed  Google Scholar 

  16. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, et al., Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4, J Exp Med 195(1), 99–111 (2002).

    PubMed  Google Scholar 

  17. Turley EA, Noble PW, Bourguignon LY, Signaling properties of hyaluronan receptors, J Biol Chem 277(7), 4589–92 (2002).

    PubMed  Google Scholar 

  18. Markwald RR, Krook JM, Kitten GT, Runyan RB, Endocardial cushion tissue development: Structural analyses on the attachment of extracellular matrix to migrating mesenchymal cell surfaces, Scan Electron Microsc 261–74 (1981).

  19. Bernanke DH, Markwald RR, Effects of hyaluronic acid on cardiac cushion tissue cells in collagen matrix cultures, Tex Rep Biol Med 39, 271–85 (1979).

    PubMed  Google Scholar 

  20. Baldwin HS, Lloyd TR, Solursh M, Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ, Circ Res 74(2), 244–52 (1994).

    PubMed  Google Scholar 

  21. Ferencz C, Boughman JA, Congenital heart disease in adolescents and adults. Teratology, genetics, and recurrence risks, Cardiol Clin 11(4), 557–67 (1993).

    PubMed  Google Scholar 

  22. Pierpont ME, Markwald RR, Lin AE, Genetic aspects of atrioventricular septal defects, Am J Med Genet 97, 289–96 (2000).

    PubMed  Google Scholar 

  23. Camenisch TD, Schroeder JA, Bradley J, Klewer SE, McDonald JA, Heart-valve mesenchyme formation is dependent on hyaluronan-augmented activation of ErbB2 ErbB3 receptors, Nat Med 8(8), 850–5 (2002).

    PubMed  Google Scholar 

  24. Lakkis MM, Epstein JA, Neurofibromin modulation of ras activity is required for normal endocardial-mesenchymal transformation in the developing heart, Development 125(22), 4359–67 (1998).

    PubMed  Google Scholar 

  25. Bourguignon LY, Zhu H, Zhou B, Dedrich F, Singleton PA, Hung MC, Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth, J Biol Chem 276(52), 48679–92 (2001).

    PubMed  Google Scholar 

  26. Bourguignon LY, Zhu H, Shao L, Chen YW, CD44 interaction with c-Src kinase promotes cortactin-mediated cytoskeleton function and hyaluronic acid-dependent ovarian tumor cell migration, J Biol Chem 276(10), 7327–36 (2001).

    PubMed  Google Scholar 

  27. Sherman LS, Rizvi TA, Karyala S, Ratner N, CD44 enhances neuregulin signaling by Schwann cells, J Cell Biol 150(5), 1071–84 (2000).

    PubMed  Google Scholar 

  28. Meyer D, Birchmeier C, Multiple essential functions of neuregulin in development, Nature 378(6555), 386–90 (1995).

    PubMed  Google Scholar 

  29. Lee H, Akita RW, Sliwkowski MX, Maihle NJ, A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulinstimulated activation of ErbB2, ErbB3, and ErbB4, Cancer Res 61(11), 4467–73 (2001).

    PubMed  Google Scholar 

  30. Camenisch TD, Molin DG, Person A, Runyan RB, Gittenbergerde Groot AC, McDonald JA, et al., Temporal and Distinct TGFbeta ligand requirements during mouse and avian endocardial cushion morphogenesis, Dev Biol 248(1), 170–81 (2002).

    PubMed  Google Scholar 

  31. Justman QA, Clinton GM, Herstatin, an autoinhibitor of the human epidermal growth factor receptor 2 tyrosine kinase, modulates epidermal growth factor signaling pathways resulting in growth arrest, J Biol Chem 277(23), 20618–24 (2002).

    PubMed  Google Scholar 

  32. Azios NG, Romero FJ, Denton MC, Doherty JK, Clinton GM, Expression of herstatin, an autoinhibitor of HER-2/neu, inhibits transactivation of HER-3 by HER-2 and blocks EGF activation of the EGF receptor, Oncogene 20(37), 5199–209 (2001).

    PubMed  Google Scholar 

  33. Schmits R, Filmus J, Gerwin N, Senaldi G, Kiefer F, Kundig T, et al., CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity, Blood 90(6), 2217–33 (1997).

    PubMed  Google Scholar 

  34. Culty M, Miyake K, Kincade PW, Sikorski E, Butcher EC, Underhill C, et al., The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins, J Cell Biol 111(6 Pt 1), 2765–74 (1990).

    PubMed  Google Scholar 

  35. Akiyama Y, Jung S, Salhia B, Lee S, Hubbard S, Taylor M, et al., Hyaluronate receptors mediating glioma cell migration and proliferation, J Neurooncol 53(2), 115–7 (2001).

    PubMed  Google Scholar 

  36. Khoursheed M, Mathew TC, Makar RR, Sonia L, Abul H, Asfar S, et al., Expression of CD44s in human colorectal cancer, Pathol Oncol Res 8(3), 170–4 (2002).

    PubMed  Google Scholar 

  37. Kong QY, Liu J, Chen XY, Wang XW, Sun Y, Li H, Differential expression patterns of hyaluronan receptors CD44 and RHAMM in transitional cell carcinomas of urinary bladder, Oncol Rep 10(1), 51–5 (2003).

    PubMed  Google Scholar 

  38. Aaltomaa S, Lipponen P, Tammi R, Tammi M, Viitanen J, Kankkunen JP, et al., Strong stromal hyaluronan expression is associated with PSA recurrence in local prostate cancer, Urol Int 69(4), 266–72 (2002).

    PubMed  Google Scholar 

  39. Jojovic M, Delpech B, Prehm P, Schumacher U, Expression of hyaluronate and hyaluronate synthase in human primary tumours and their metastases in scid mice, Cancer Lett 188(1/2), 181–9 (2002).

    PubMed  Google Scholar 

  40. Tsuchiya N, Kondo Y, Takahashi A, Pawar H, Qian J, Sato K, Lieber MM, Jenkins RB, Mapping and gene expression profile of the minimally overrepressented 8q24 region in prostate cancer, Am J Pathol 160, 1799–806 (2002).

    PubMed  Google Scholar 

  41. Simpson MA, Wilson CM, Furcht LT, Spicer AP, Oegema TR Jr, McCarthy JB, Manipulation of hyaluronan synthase expression in prostate adenocarcinoma cells alters pericellular matrix retention and adhesion to bone marrow endothelial cells, J Biol Chem 277(12), 10050–7 (2002).

    PubMed  Google Scholar 

  42. Ramsden CA, Bankier A, Brown TJ, Cowen PS, Frost GI, McCallum DD, Studdert VP, Fraser JR, Anew disorder of hyaluronan metabolism associated with generalized folding and thickening of the skin, J Pediatr 136, 62–8 (2000).

    PubMed  Google Scholar 

  43. Natowicz MR, Short MP, Wang Y, Dickersin GR, Gebhardt MC, Rosenthal DI, et al., Clinical and biochemical manifestations of hyaluronidase deficiency, N Engl J Med 335(14), 1029–33 (1996).

    PubMed  Google Scholar 

  44. Triggs-Raine B, Salo TJ, Zhang H, Wicklow BA, Natowicz MR, Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX, Proc Natl Acad Sci USA 96(11), 6296–300 (1999).

    PubMed  Google Scholar 

  45. Csoka AB, Frost GI, Stern R, The six hyaluronidase-like genes in the human and mouse genomes, Matrix Biol 20(8), 499–508 (2001).

    PubMed  Google Scholar 

  46. Zheng Y, Deng X, Zhao Y, Zhang H, Martin-DeLeon PA, Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation, MammGenome 12(11), 822–9 (2001).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Salt Lake City Veterans Administration Health Care System and, University of Utah, 500 Foothill Drive, Salt Lake City, UT, 84148, USA

    John A. McDonald

  2. Department of Pharmacology, The University of Arizona Health Sciences Center, College of Pharmacy, 1703 E. Mabel St., PO Box 210207, Tucson, AZ, 85721-0207, USA

    Todd D. Camenisch

Authors
  1. John A. McDonald
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Todd D. Camenisch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to John A. McDonald.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDonald, J.A., Camenisch, T.D. Hyaluronan: Genetic insights into the complex biology of a simple polysaccharide. Glycoconj J 19, 331–339 (2002). https://doi.org/10.1023/A:1025369004783

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025369004783

Search

Navigation