Skip to main content
SpringerLink
Log in

The nematode Caenorhabditis elegans as a model to study the roles of proteoglycans

  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

The nematode Caenorhabditis elegans is a powerful animal model for exploring the genetic basis of metazoan development. Recent genetic and biochemical studies have revealed that the molecular machinery of glycosaminoglycan (GAG) biosynthesis and modification is highly conserved between C. elegans and mammals. In addition, genetic studies have implicated GAGs in vulval morphogenesis and zygotic cytokinesis. The extensive knowledge of C. elegans biology, including its elucidated cell lineage, together with the completed and well annotated DNA sequence and availability of reverse genetic tools, provide a platform for studying the functions of proteoglycans and their GAG modification. 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. Genome sequence of the nematode C. elegans: A platform for investigating biology. The C. elegans sequencing consortium, Science 282, 2012–8 (1998).

    Google Scholar 

  2. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC, Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans, Nature 391, 806–11 (1998).

    PubMed  Google Scholar 

  3. Kornfeld K, Vulval development in Caenorhabditis elegans, Trends Genet 13, 55–61 (1997).

    PubMed  Google Scholar 

  4. Herman T, Hartwieg E, Horvitz HR, sqv mutants of Caenorhabditis elegans are defective in vulval epithelial invagination, Proc Natl Acad Sci USA 96, 968–73 (1999).

    PubMed  Google Scholar 

  5. Herman T, Horvitz HR, Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway, Proc Natl Acad Sci USA 96, 974–9 (1999).

    PubMed  Google Scholar 

  6. Berninsone PM, Hirschberg CB, Nucleotide sugar transporters of the Golgi apparatus, Curr Opin Struct Biol 10, 542–7 (2000).

    PubMed  Google Scholar 

  7. Berninsone P, Hwang HY, Zemtseva I, Horvitz HR, Hirschberg CB, SQV-7, a protein involved in Caenorhabditis elegans epithelial invagination and early embryogenesis, transports UDP-glucuronic acid, UDP-N-acetylgalactosamine, and UDP-galactose, Proc Natl Acad Sci USA 98, 3738–43 (2001).

    PubMed  Google Scholar 

  8. Bulik DA, Wei G, Toyoda H, Kinoshita-Toyoda A, Waldrip WR, Esko JD, Robbins PW, Selleck SB, sqv-3,-7, and-8, a set of The nematode Caenorhabditis elegans as a model to study the roles of proteoglycans 329 genes affecting morphogenesis in Caenorhabditis elegans, encode enzymes required for glycosaminoglycan biosynthesis, Proc Natl Acad Sci USA 97, 10838–43 (2000).

    PubMed  Google Scholar 

  9. Hwang HY, Horvitz HR, The SQV-1 UDP-glucuronic acid decarboxylase and the SQV-7 nucleotide-sugar transporter may act in the Golgi apparatus to affect Caenorhabditis elegans vulval morphogenesis and embryonic development. Proc Natl Acad Sci USA 99, 14218–23 (2002).

    PubMed  Google Scholar 

  10. Hwang HY, Olson SK, Brown JR, Esko HD, Horvitz HR, The C. elegans genes sqv-2 and sqv-6, which are required tor vulval morphogenesis, encode glycosaminoglycan galactosyltransferase II and xylosyltransferase, J Biol Chem 278, (2003).

  11. Hwang HY, Horvitz HR, The Caenorhabditis elegans vulval morphogenesis gene sqv-4 encodes a UDP-glucose dehydrogenase that is temporally and spatially regulated, Proc Natl Acad Sci USA 99, 14224–9 (2002).

    PubMed  Google Scholar 

  12. Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R, Carrozzo R, Maestrini E, Pieretti M, Taillon-Miller P, et al., A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules, Nature 353, 529–36 (1991).

    PubMed  Google Scholar 

  13. Legouis R, Hardelin JP, Levilliers J, Claverie JM, Compain S, Wunderle V, Millasseau P, Le Paslier D, Cohen D, Caterina D, et al., The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules, Cell 67, 423–35 (1991).

    PubMed  Google Scholar 

  14. Bulow HE, Berry KL, Topper LH, Peles E, Hobert O, Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome gene kal-1, Proc Natl Acad Sci USA 99, 6346–51 (2002).

    PubMed  Google Scholar 

  15. Yamada S, Van Die I, Van den Eijnden DH, Yokota A, Kitagawa H, Sugahara K, Demonstration of glycosaminoglycans in Caenorhabditis elegans, FEBS Lett 459, 327–31 (1999).

    PubMed  Google Scholar 

  16. Toyoda H, Kinoshita-Toyoda A, Selleck SB, Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo, J Biol Chem 275, 2269–75 (2000).

    PubMed  Google Scholar 

  17. Schimpf J, Sames K, Zwilling R, Proteoglycan distribution pattern during aging in the nematode Caenorhabditis elegans: An ultrastructural histochemical study, Histochem J 31, 285–92 (1999).

    PubMed  Google Scholar 

  18. Beeber C, Kieras FJ, Characterization of the chondroitin sulfates in wild type Caenorhabditis elegans, Biochem Biophys Res Commun 293, 1374–6 (2002).

    PubMed  Google Scholar 

  19. Yamada S, Okada Y, Ueno M, Iwata S, Deepa SS, Nishimura S, Fujita M, Van Die I, Hirabayashi Y, Sugahara K, Determination of the glycosaminoglycan-protein linkage region oligosaccharide structures of proteoglycans from Drosophila melanogaster and Caenorhabditis elegans, J Biol Chem 277, 31877–86 (2002).

    PubMed  Google Scholar 

  20. Guerardel Y, Balanzino L, Maes E, Leroy Y, Coddeville B, Oriol R, Strecker G, The nematode Caenorhabditis elegans synthesizes unusual O-linked glycans: Identification of glucose-substituted mucin-type O-glycans and short chondroitin-like oligosaccharides, Biochem J 357, 167–82 (2001).

    PubMed  Google Scholar 

  21. Gotting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K, Molecular cloning and expression of human UDP-D-Xylose:proteoglycan core protein beta-D-xylosyltransferase and its first isoform XT-II, J Mol Biol 304, 517–28 (2000).

    PubMed  Google Scholar 

  22. Wilson IB, Functional characterization of Drosophila melanogaster peptide O-xylosyltransferase, the key enzyme for proteoglycan chain initiation and member of the core 2/I Nacetylglucosaminyltransferase family, J Biol Chem 277, 21207–12 (2002).

    PubMed  Google Scholar 

  23. Almeida R, Levery SB, Mandel U, Kresse H, Schwientek T, Bennett EP, Clausen H, Cloning and expression of a proteoglycan UDP-galactose:beta-xylose beta1,4-galactosyltransferase I. A seventh member of the human beta 4-galactosyltransferase gene family, J Biol Chem 274, 26165–71 (1999).

    PubMed  Google Scholar 

  24. Kitagawa H, Tone Y, Tamura J, Neumann KW, Ogawa T, Oka S, Kawasaki T, Sugahara K, Molecular cloning and expression of glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans, J Biol Chem 273, 6615–8 (1998).

    PubMed  Google Scholar 

  25. Esko JD, Selleck SB, ORDER OUT OF CHAOS: Assembly of ligand binding sites in heparan sulfate, Annu Rev Biochem 71, 435–71 (2002).

    PubMed  Google Scholar 

  26. Sugahara K, Kitagawa H, Recent advances in the study of the biosynthesis and functions of sulfated glycosaminoglycans, Curr Opin Struct Biol 10, 518–27 (2000).

    PubMed  Google Scholar 

  27. Kitagawa H, Shimakawa H, Sugahara K, The tumor suppressor EXT-like gene EXTL2 encodes an alpha1, 4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and Nacetylglucosamine to the common glycosaminoglycan-protein linkage region. The key enzyme for the chain initiation of heparan sulfate, J Biol Chem 274, 13933–7 (1999).

    PubMed  Google Scholar 

  28. Kim BT, Kitagawa H, Tamura J, Saito T, Kusche-Gullberg M, Lindahl U, Sugahara K, Humantumor suppressorEXTgene family members EXTL1 and EXTL3 encode alpha 1,4-N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis, Proc Natl Acad Sci USA 98, 7176–81 (2001).

    PubMed  Google Scholar 

  29. Senay C, Lind T, Muguruma K, Tone Y, Kitagawa H, Sugahara K, Lidholt K, Lindahl U, Kusche-Gullberg M, The EXT1/EXT2 tumor suppressors: Catalytic activities and role in heparan sulfate biosynthesis, EMBO Rep 1, 282–6 (2000).

    PubMed  Google Scholar 

  30. Kitagawa H, Egusa N, Tamura JI, Kusche-Gullberg M, Lindahl U, Sugahara K, rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes encodes a novel alpha1,4-Nacetylglucosaminyltransferase involved in the biosynthetic initiation and elongation of heparan sulfate, J Biol Chem 276, 4834–8 (2001).

    PubMed  Google Scholar 

  31. Kitagawa H, Uyama T, Sugahara K, Molecular cloning and expression of a human chondroitin synthase, J Biol Chem 276, 38721–6 (2001).

    PubMed  Google Scholar 

  32. Uyama T, Kitagawa H, Tamura Ji J, Sugahara K, Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase: The key enzyme for chain initiation and elongation of chondroitin/dermatan sulfate on the protein linkage region tetrasaccharide shared by heparin/heparan sulfate, J Biol Chem 277, 8841–6 (2002).

    PubMed  Google Scholar 

  33. Rogalski TM, Williams BD, Mullen GP, Moerman DG, Products of the unc-52 gene in Caenorhabditis elegans are homologous to the core protein of the mammalian basement membrane heparan sulfate proteoglycan, Genes Dev 7, 1471–84 (1993).

    PubMed  Google Scholar 

  34. Mullen GP, Rogalski TM, Bush JA, Gorji PR, Moerman DG, Complex patterns of alternative splicing mediate the spatial and temporal distribution of perlecan/UNC-52 in Caenorhabditis elegans, Mol Biol Cell 10, 3205–21 (1999).

    PubMed  Google Scholar 

  35. Maeda I, Kohara Y, Yamamoto M, Sugimoto A, Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi, Current Biology 11, 171–6 (2001).

    PubMed  Google Scholar 

  36. Morio H, Honda Y, Toyoda H, Nakajima M, Kurosawa H, Shirasawa T, EXTgene family member rib-2 is essential for embryonic development and heparan sulfate biosynthesis in Caenorhabditis elegans, Biochem Biophys Res Commun 301(2), 317–23 (2003).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cell Biology, Boston University School of Dental Medicine, Boston, MA, 02118, USA

    Patricia M. Berninsone & Carlos B. Hirschberg

Authors
  1. Patricia M. Berninsone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carlos B. Hirschberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carlos B. Hirschberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berninsone, P.M., Hirschberg, C.B. The nematode Caenorhabditis elegans as a model to study the roles of proteoglycans. Glycoconj J 19, 325–330 (2002). https://doi.org/10.1023/A:1025364820713

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1025364820713

Search

Navigation