Abstract
Defects in glycosaminoglycan biosynthesis disrupt animal development and can cause human disease1,2,3,4. So far much of the focus on glycosaminoglycans has been on heparan sulphate. Mutations in eight squashed vulva (sqv) genes in Caenorhabditis elegans cause defects in cytokinesis during embryogenesis and in vulval morphogenesis during postembryonic development5,6. Seven of the eight sqv genes have been shown to control the biosynthesis of the glycosaminoglycans chondroitin and heparan sulphate6,7,8,9,10,11. Here we present the molecular identification and characterization of the eighth gene, sqv-5. This gene encodes a bifunctional glycosyltransferase that is probably localized to the Golgi apparatus and is responsible for the biosynthesis of chondroitin but not heparan sulphate. Our findings show that chondroitin is crucial for both cytokinesis and morphogenesis during C. elegans development.
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References
Quentin, E., Gladen, A., Roden, L. & Kresse, H. A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc. Natl Acad. Sci. USA 87, 1342–1346 (1990)
Perrimon, N. & Bernfield, M. Specificities of heparan sulphate proteoglycans in developmental processes. Nature 404, 725–728 (2000)
Zak, B. M., Crawford, B. E. & Esko, J. D. Hereditary multiple exostoses and heparan sulfate polymerization. Biochim. Biophys. Acta 1573, 346–355 (2002)
Schwartz, N. B. & Domowicz, M. Chondrodysplasias due to proteoglycan defects. Glycobiology 12, 57R–68R (2002)
Herman, T., Hartwieg, E. & Horvitz, H. R. sqv mutants of Caenorhabditis elegans are defective in vulval epithelial invagination. Proc. Natl Acad. Sci. USA 96, 968–973 (1999)
Hwang, H.-Y. & Horvitz, H. R. The SQV-1 UDP-glucuronic acid decarboxylase and the SQV-7 nucleotide-sugar transporter may act in the Golgi apparatus to affect C. elegans vulval morphogenesis and embryonic development. Proc. Natl Acad. Sci. USA 99, 14218–14223 (2002)
Herman, T. & Horvitz, H. R. Three proteins involved in Caenorhabditis elegans vulval invagination are similar to components of a glycosylation pathway. Proc. Natl Acad. Sci. USA 96, 974–979 (1999)
Bulik, D. A. et al. sqv-3, -7, and -8, a set of genes affecting morphogenesis in Caenorhabditis elegans, encode enzymes required for glycosaminoglycan biosynthesis. Proc. Natl Acad. Sci. USA 97, 10838–108343 (2000)
Berninsone, P., Hwang, H. Y., Zemtseva, I., Horvitz, H. R. & Hirschberg, C. B. 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, 3738–3743 (2001)
Hwang, H.-Y. & Horvitz, H. R. The C. elegans vulval morphogenesis gene sqv-4 encodes a UDP-glucose dehydrogenase that is temporally and spatially regulated. Proc. Natl Acad. Sci. USA 99, 14224–14229 (2002)
Hwang, H.-Y., Olson, S. K., Brown, J. R., Esko, J. D. & Horvitz, H. R. The C. elegans genes sqv-2 and sqv-6, which are involved in vulval morphogenesis, encode glycosaminoglycan galactosyltransferase II and xylosyltransferase. J. Biol. Chem. 278, 11735–11738 (2003)
Comper, W. D. & Laurent, T. C. Physiological function of connective tissue polysaccharides. Physiol. Rev. 58, 255–315 (1978)
Ruoslahti, E. Structure and biology of proteoglycans. Annu. Rev. Cell Biol. 4, 229–255 (1988)
Esko, J. D. & Selleck, S. B. Order out of chaos: assembly of ligand binding sites in heparan sulfate. Annu. Rev. Biochem. 71, 435–471 (2002)
Silbert, J. E. & Sugumaran, G. Biosynthesis of chondroitin/dermatan sulfate. Intl Union Biochem. Mol. Biol. Life 54, 177–186 (2002)
Austin, C. R. Fertilization (New Jersey, Prentice Hall, Englewood Cliffs, 1965)
Almeida, R. et al. Cloning and expression of a proteoglycan UDP-galactose: β-xylose β1,4-galactosyltransferase I. J. Biol. Chem. 274, 26165–26171 (1999)
Okajima, T., Fukumoto, S., Furukawa, K. & Urano, T. Molecular basis for the progeroid variant of Ehlers–Danlos syndrome. J. Biol. Chem. 274, 28841–28844 (1999)
Kitagawa, H., Uyama, T. & Sugahara, K. Molecular cloning and expression of a human chondroitin synthase. J. Biol. Chem. 276, 38721–38726 (2001)
Uyama, T., Kitagawa, H., Tamura Ji, J. & Sugahara, K. Molecular cloning and expression of human chondroitin N-acetylgalactosaminyltransferase. J. Biol. Chem. 277, 8841–8846 (2002)
Yamada, S. et al. Demonstration of glycosaminoglycans in Caenorhabditis elegans. FEBS Lett. 459, 327–331 (1999)
Toyoda, H., Kinoshita-Toyoda, A. & Selleck, S. B. Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumour suppressors, affects heparan sulfate in vivo. J. Biol. Chem. 275, 2269–2275 (2000)
Timmons, L. & Fire, A. Specific interference by ingested dsRNA. Nature 395, 854 (1998)
Lane, M. C., Koehl, M. A., Wilt, F. & Keller, R. A role for regulated secretion of apical extracellular matrix during epithelial invagination in the sea urchin. Development 117, 1049–1060 (1993)
Ellis, R. E. & Kimble, J. The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans. Genetics 139, 561–577 (1995)
Jansen, G., Hazendonk, E., Thijssen, K. L. & Plasterk, R. H. Reverse genetics by chemical mutagenesis in Caenorhabditis elegans. Nature Genet. 17, 119–121 (1997)
Nagasawa, K., Inoue, Y. & Kamata, T. Solvolytic desulfation of glycosaminoglycuronan sulfates with dimethyl sulfoxide containing water or methanol. Carbohydr. Res. 58, 47–55 (1977)
Fritz, T. A., Gabb, M. M., Wei, G. & Esko, J. D. Two N-acetylglucosaminyltransferases catalyze the biosynthesis of heparan sulfate. J. Biol. Chem. 269, 28809–28814 (1994)
Wei, G. et al. Location of the glucuronosyltransferase domain in the heparan sulfate copolymerase EXT1 by analysis of Chinese hamster ovary cell mutants. J. Biol. Chem. 275, 27733–27740 (2000)
Esko, J. D. in Current Protocols in Molecular Biology (ed. Ausubel, F.) 17.2.1–17.2.9 (John Wiley and Sons, New York, 1993)
Acknowledgements
We thank B. Castor for help with DNA sequencing; Y. Kohara for the cDNA clones yk20dy and yk21g9; A. Coulson for cosmids; J. Brown for the GlcAβ1,3Gal-O-NM acceptor; B. Zak for N-acetylheparosan acceptor; the Glycotechnology Core at UCSD (supported by an NIH grant) for the preparation of UDP-[1-3H]GlcA; and B. Galvin and I. Perez de la Cruz for reading the manuscript. This work was supported by NIH grants (to H.R.H. and J.D.E.). S.K.O. was supported by an NIH training grant. H.R.H. is an Investigator of the Howard Hughes Medical Institute.
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Hwang, HY., Olson, S., Esko, J. et al. Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis. Nature 423, 439–443 (2003). https://doi.org/10.1038/nature01634
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DOI: https://doi.org/10.1038/nature01634
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