Biosynthetic pathways for differential expression of functional chondroitin sulfate and heparan sulfate

Handbook of Carbohydrate Engineering

Volumn , Issue , 2005, Pages 289-324

  Mizumoto, Shuji ^a   Uyama, Toru ^a   Mikami, Tadahisa ^a   Kitagawa, Hiroshi ^a   Sugahara, Kazuyuki ^a  

^a KOBE PHARMACEUTICAL UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84896762510     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (186)

1. Esko, J.D. and Selleck, S.B., Order out of chaos: assembly of ligand binding sites in heparan sulfate, Annu. Rev. Biochem., 71, 435, 2002.
2. Gotting, C., Kuhn, J., Zahn, R., Brinkmann, T., and Kleesiek, K., Molecular cloning and expression of human UDP-D-xylose:proteoglycan core protein jS-D-xylosyltrans-ferase and its first isoform XT-II, J. Mol. Biol., 304, 517, 2000.
3. Prydz, K. and Dalen, K.T., Synthesis and sorting of proteoglycans, J. Cell Sci., 113, 193, 2000.
4. Okajima, T., Yoshida, K., Kondo, T., and Furukawa, K., Human homolog of Caenorhabditis elegans sqv-3 gene is galactosyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans, J. Biol. Chem., 274, 22915, 1999.
5. Almeida, R., Levery, S.B., Mandel, U., Kresse, H., Schwientek, T., Bennett, E. P., and Clausen, H., Cloning and expression of a proteoglycan UDP-galactose: S-xylose S1,4-galactosyltransferase I: A seventh member of the human S4-galactosyltrans-ferase gene family, J. Biol. Chem., 274, 26165, 1999.
6. Bai, X., Zhou, D., Brown, J.R., Crawford, B.E., Hennet, T., and Esko, J.D., Biosynthesis of the linkage region of glycosaminoglycans: cloning and activity of galactosyltransferase II, the sixth member of the S1,3-galactosyltransferase family (S3GalT6), J. Biol. Chem., 276, 48189, 2001.
7. Kitagawa, H., Tone, Y., Tamura, J., Newmann, K.W., Ogawa, T., Oka, S., Kawasaki, T., and 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, 1998.
8. Wei, G., Bai, X., Sarkar, A.K., and Esko, J.D., Formation of HNK-1 determinants and the glycosaminoglycan tetrasaccharide linkage region by UDP-GlcUA: galactose S1,3-glucuronosyltransferases, J. Biol. Chem., 274, 7857, 1999.
9. Terayama, K., Oka, S., Seiki, T., Miki, Y., Nakamura, A., Kozutsumi, Y., Takio, K., and Kawasaki, T., Cloning and functional expression of a novel glucuronyltransferase involved in the biosynthesis of the carbohydrate epitope HNK-1, Proc. Natl. Acad. Sci. USA, 94, 6093, 1997.
10. Tone, Y., Kitagawa, H., Imiya, K., Oka, S., Kawasaki, T., and Sugahara, K., Characterization of recombinant human glucuronyltransferase I involved in the biosynthesis of the glycosaminoglycan-protein linkage region of proteoglycans, FEBS Lett., 459, 415, 1999.
11. Sugahara, K. and Kitagawa, H., Recent advances in the study of the biosynthesis and functions of sulfated glycosaminoglycans, Curr. Opin. Struct. Biol., 10, 518, 2000.
12. Moses, J., Oldberg, A., and Fransson, L.-A., Initiation of galactosaminoglycan biosynthesis: separate galactosylation and dephosphorylation pathways for phospho-xylosylated decorin protein and exogenous xyloside, Eur. J. Biochem., 260, 879, 1999.
13. Sugahara, K. and Yamada, S., Structure and function of oversulfated chondroitin sulfate variants: unique sulfation patterns and neuroregulatory activities, Trends Glycosci. Glycotechnol., 12, 321, 2000.
14. Quentin, E., Gladen, A., Roden, L., and 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, 1990.
15. Okajima, T., Fukumoto, S., Furukawa, K., Urano, T., and Furukawa, K., Molecular basis for the progeroid variant of Ehlers-Danlos syndrome: identification and characterization of two mutations in galactosyltransferase I gene, J. Biol. Chem., 274, 28841, 1999.
16. Nakamura, Y., Haines, N., Chen, J., Okajima, T., Furukawa, K., Urano, T., Stanley, P., Irvine, K.D., and Furukawa, K., Identification of a Drosophila gene encoding xylo-sylprotein j84-galactosyltransferase that is essential for the synthesis of glycosamino-glycans and for morphogenesis, J. Biol. Chem., 277, 46280, 2002.
17. Herman, T., Hartwieg, E., and Horvitz, H.R., sqv mutants of Caenorhabditis elegans are defective in vulval epithelial invagination, Proc. Natl. Acad. Sci. USA, 96, 968, 1999.
18. Herman, T. and 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, 1999.
19. Sugahara, K., Mikami, T., Uyama, T., Mizuguchi, S., Nomura, K., and Kitagawa, H., Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate, Curr. Opin. Struct. Biol., 13, 612, 2003.
20. Bulik, D.A., Wei, G., Toyoda, H., Kinoshita-Toyoda, A., Waldrip, W.R., Esko, J.D., Robbins, P.W., and Selleck, S.B., 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, 2000.
21. Mizuguchi, S., Uyama, T., Kitagawa, H., Nomura, K.H., Dejima, K., Gengyo-Ando, K., Mitani, S., Sugahara, K., and Nomura, K., Chondroitin proteoglycans are involved in cell division ofCaenorhabditis elegans, Nature, 423, 443, 2003.
22. Hwang, H.-Y., Olsen, S.K., Esko, J.D., and Horvitz, H.R., Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis, Nature, 423, 439, 2003.
23. Silbert, J.E. and Sugumaran, G., Biosynthesis of chondroitin/dermatan sulfate, IUBMB Life, 54, 177, 2002.
24. Kitagawa, H., Uyama, T., and Sugahara, K., Molecular cloning and expression of a human chondroitin synthase, J. Biol. Chem., 276, 38721, 2001.
25. Kitagawa, H., Izumikawa, T., Uyama, T., and Sugahara, K., Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chon-droitin polymerization, J. Biol. Chem., 278, 23666, 2003.
26. Uyama, T., Kitagawa, H., Tamura, J., and 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, 2002.
27. Gotoh, M., Sato, T., Akashima, T., Iwasaki, H., Kameyama, A., Mochizuki, H., Yada, T., Inaba, N., Zhang, Y., Kikuchi, N., Kwon, Y.-D., Togayachi, A., Kudo, T., Nishihara, S., Watanabe, H., Kimata, K., and Narimatsu, H., Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetyl-galactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis, J. Biol. Chem., 277, 38189, 2002.
28. Uyama, T., Kitagawa, H., Tanaka, J., Tamura, J., Ogawa, T., and Sugahara, K., Molecular cloning and expression of a second chondroitin N-acetylgalactosaminyltransferase involved in the initiation and elongation of chondroitin/dermatan sulfate, J. Biol. Chem., 278, 3072, 2003.
29. Sato, T., Gotoh, M., Kiyohara, K., Akashima, T., Iwasaki, H., Kameyama, A., Mochizuki, H., Yada, T., Inaba, N., Togayachi, A., Kudo, T., Asada, M., Watanabe, H., Imamura, T., Kimata, K., and Narimatsu, H., Differential roles of two N-acetylgalac-tosaminyltransferases, CSGalNAcT-1, and a novel enzyme, CSGalNAcT-2: initiation and elongation in synthesis of chondroitin sulfate, J. Biol. Chem., 278, 3063, 2003.
30. Gotoh, M., Yada, T., Sato, T., Akashima, T., Iwasaki, H., Mochizuki, H., Inaba, N., Togayachi, A., Kudo, T., Watanabe, H., Kimata, K., and Narimatsu, H., Molecular cloning and characterization of a novel chondroitin sulfate glucuronyltransferase that transfers glucuronic acid to N-acetylgalactosamine, J. Biol. Chem., 277, 38179, 2002.
31. Liaw, P.C., Becker, D.L., Stafford, A.R., Fredenburgh, J.C., and Weitz, J.I., Molecular basis for the susceptibility of fibrin-bound thrombin to inactivation by heparin cofactor II in the presence of dermatan sulfate but not heparin, J. Biol. Chem., 276, 20959, 2001.
32. Garcia-Garcia, M.J. and Anderson, K.V., Essential role of glycosaminoglycans in fgf signaling during mouse gastrulation, Cell, 114, 727, 2003.
33. Walsh, E.C. and Stainier, D.Y.R., UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish, Science, 293, 1670, 2001.
34. Binari, R.C., Staveley, B.E., Johnson, W.A., Godavarti, R., Sasisekharan, R., and Manoukian, A.S., Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling, Development, 124, 2623, 1997.
35. Haerry, T.E., Heslip, T.R., Marsh, J.L., and O’Connor, M.B., Defects in glucuronate biosynthesis disrupt wingless signaling inDrosophila, Development, 124, 3055, 1997.
36. Häcker, U., Lin, X., and Perrimon, N., The Drosophila sugarless gene modulates wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis, Development, 124, 3565, 1997.
37. Berninsone, P., Hwang, H.-Y., Zemtseve, I., Horvitz, H.R., and Hirschberg, C.B., Proc. SQV-7, a protein involved in Caenorhabditis elegans epithelial invagination and early embryogenesis, transports UDP-glucuronic acid, UDP-N-acetylgalac-tosamine, and UDP-galactose, Natl. Acad. Sci. USA, 98, 3738, 2001.
38. Selva, E.M., Hong, K., Baeg, G.-H., Beverley, S.M., Turco, S.J., Perrimon, N., and Häcker, U., Dual role of the fringe connection gene in both heparan sulphate and fringe-dependent signalling events, Nat. Cell Biol, 3, 809, 2001.
39. Goto, S., Taniguchi, M., Muraoka, M., Toyoda, H., Sado, Y., Kawakita, M., and Hayashi, S., UDP-sugar transporter implicated in glycosylation and processing of Notch, Nat. Cell Biol, 3, 816, 2001.
40. Deepa, S.S., Umehara, Y., Higashiyama, S., Itoh, N., and Sugahara, K., Specific molecular interactions of oversulfated chondroitin sulfate E with various heparinbinding growth factors: implications as a physiological binding partner in the brain and other tissues, J. Biol. Chem, 277, 43707, 2002.
41. Kusche-Gullberg, M., and Kjellén, L., Sulfotransferases in glycosaminoglycan biosynthesis, Curr. Opin. Struct. Biol., 13, 605, 2003.
42. Fukuta, M., Kobayashi, Y., Uchimura, K., Kimata, K., and Habuchi, O., Molecular cloning and expression of human chondroitin 6-sulfotransferase, Biochim. Biophys. Acta, 1399, 57, 1998.
43. Uchimura, K., Kadomatsu, K., Nishimura, H., Muramatsu, H., Nakamura, E., Kurosawa, N., Habuchi, O., El-Fasakhany, F.M., Yoshikai, Y., and Muramatsu, T., Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates, J. Biol. Chem, 277, 1443, 2002.
44. Hiraoka, N., Nakagawa, H., Ong, E., Akama, T.O., Fukuda, M.N., and Fukuda, M., Molecular cloning and expression of two distinct human chondroitin 4-O-sulfotrans-ferases that belong to the HNK-1 sulfotransferase gene family, J. Biol. Chem., 275, 20188, 2000.
45. Kang, H.-G., Evers, M. R., Xia, G., Baenziger, J.U., and Schachner, M., Molecular cloning and characterization of chondroitin-4-O-sulfotransferase-3: a novel member of the HNK-1 family of sulfotransferases, J. Biol. Chem., 277, 34766, 2002.
46. Evers, M.R., Xia, G., Kang, H.-G., Schachner, M., and Baenziger, J.U., Molecular cloning and characterization of a dermatan-specific N-acetylgalactosamine 4-O-sul-fotransferase, J. Biol. Chem, 276, 36344, 2001.
47. Mikami, T., Mizumoto, S., Kago, N., Kitagawa, H., and Sugahara, K., Specificities of three distinct human chondroitin/dermatan N-acetylgalactosamine 4-O-sulfotrans-ferases demonstrated using partially desulfated dermatan sulfate as an acceptor: implication of differential roles in dermatan sulfate biosynthesis, J. Biol. Chem, 278, 36115, 2003.
48. Kobayashi, M., Sugumaran, G., Liu, J., Shworak, N.W., Silbert, J.E., and Rosenberg, R.D., Molecular cloning and characterization of a Human Uronyl 2-sulfotransferase that sulfates iduronyl and glucuronyl residues in dermatan/chondroitin sulfate, J. Biol. Chem, 274, 10474, 1999.
49. Ohtake, S., Ito, Y., Fukuta, M., and Habuchi, O., Human N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase cDNA is related to Human B Cell recombination activating gene-associated gene, J. Biol. Chem, 276, 43894, 2001.
50. Venkatachalam, K. V., Human 3'-phosphoadenosine 5'-phosphosulfate (PAPS) synthase: biochemistry, molecular biology and genetic deficiency, IUBMB Life, 55, 1, 2003.
51. Superti-Figra, A., Hästbacka, J., Wilcox, W.R., Cohn, D.H., van der Harten, J.J., Rossi, A., Blau, N., Rimoin, D.L., Steinmann, B., Lander, E.S., and Gitzelmann, R., Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene, Nat. Genet., 12, 100, 1996.
52. Rossi, A., Bonaventure, J., Delezoide, A.-L., Cetta, G., and Superti-Furga, A., Undersulfation of proteoglycans synthesized by chondrocytes from a patient with achondrogenesis type 1B homozygous for an L483P substitution in the diastrophic dysplasia sulfate transporter, J. Biol. Chem., 271, 18456, 1996.
53. Li, H., Deyrup, A., Mensch, J.R., Domowicz, M., Konstantinidis, A.K., and Schwartz, N.B., The isolation and characterization of cDNA encoding the mouse bifunctional ATP sulfurylase-adenosine 5'-phosphosulfate kinase. J. Biol. Chem, 270, 29453, 1995.
54. Kurima, K., Warman, M.L., Krishnan, S., Domowicz, M., Krueger, R.C., Deyrup, A., and Schwartz, N.B., A member of a family of sulfate-activating enzymes causes murine brachymorphism, Proc. Natl. Acad. Sci. USA, 95, 8681, 1998.
55. ul Haque, M.F., King, L.M., Krakow, D., Cantor, R.M., Rusiniak, M.E., Swank, R.T., Superti-Furga, A., Haque, S., Abbas, H., Ahmad, W., Ahmad, M., and Cohn, D.H., Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse, Nat. Genet., 20, 157, 1998.
56. Lüders, F., Segawa, H., Stein, D., Selva, E.M., Perrimon, N., Turco, S.J., and Häcker, U., slalom encodes an adenosine 3'-phosphate 5'-phosphosulfate transporter essential for development inDrosophila, EMBO J., 22, 3635, 2003.
57. Kamiyama, S., Suda, T., Ueda, R., Suzuki, M., Okubo, R., Kikuchi, N., Chiba, Y., Goto, S., Toyoda, H., Saigo, K., Watanabe, H., Narimatsu, H., Jigami, Y., and Nishihara, S., Molecular cloning and identification of 3'-phosphoadenosine 5'-phos-phosulfate transporter, J. Biol. Chem., 278, 25958, 2003.
58. Schwartz, N.B. and Domowicz, M., Chondrodysplasias due to proteoglycan defects, Glycobiology, 12, 57R, 2002.
59. Lin, X. and Perrimon, N., Dally cooperates with Drosophila frizzled 2 to transduce wingless signalling, Nature, 400, 281, 1999.
60. Lin, X., Buff, E.M., Perrimon, N., and Michelson, A.M., Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development, Development, 126, 3715, 1999.
61. McCormick, C., Leduc, Y., Martindale, D., Mattison, K., Esford, L.E., Dyer, A.P., and Tufaro, F., The putative tumour suppressor EXT1 alters the expression of cell-surface heparan sulfate, Nat. Genet, 19, 158, 1998.
62. Lind, T., Tufaro, F., McCormick, C., Lindahl, U., and Lidholt, K., The putative tumor suppressors EXT1 and EXT2 Are glycosyltransferases required for the biosynthesis of heparan sulfate, J. Biol. Chem., 273, 26265, 1998.
63. McCormick, C., Duncan, G., Goutsos, T., and Tufaro, F., The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the Golgi apparatus and catalyzes the synthesis of heparan sulfate, Proc. Natl. Acad. Sci. USA, 97, 668, 2000.
64. Senay, C., Lind, T., Muguruma, K., Tone, Y., Kitagawa, H., Sugahara, K., Lidholt, K., Lindahl, U., and Kusche-Gullberg, M., The EXT1/EXT2 tumor suppressors: catalytic activities and role in heparan sulfate biosynthesis, EMBO Rep., 1, 282, 2000.
65. Kim, B. -T., Kitagawa, H., Tanaka, J., Tamura, J., and Sugahara, K., In vitro heparan sulfate polymerization: crucial roles of core protein moieties of primer substrates in addition to the EXT1-EXT2 interaction, J. Biol. Chem., 278, 41618, 2003.
66. Busse, M. and Kusche-Gullberg, M., In vitro polymerization of heparan sulfate backbone by the EXT proteins, J. Biol. Chem., 278, 41333, 2003.
67. Solomon, L., Hereditary multiple exostosis, J. Bone Joint Surg., 45, 292, 1963.
68. Leone, N.C., Shupe, J.L., Gardner, E.J., Millar, E.A., Olson, A.E., and Phillips, E.C., Hereditary multiple exostosis. A comparative human-equine-epidemiologic study, J. Hered., 78, 171, 1987.
69. Hennekam, R.C., Hereditary multiple exostosis, J. Med. Genet., 28, 262, 1991.
70. Schmale, G.A., Conrad, E.U., and Raskind, W.H., The natural history of hereditary multiple exostoses, J. Bone Joint Surg., 76, 986, 1994.
71. Luckert-Wicklund, C., Pauri, R., Johnston, D., and Hecht, J., Natural history of hereditary multiple exostoses, Am. J. Med. Genet., 55, 43, 1995.
72. Cook, A., Raskind, W., Blanton, S.H., Pauli, R.M., Gregg, R.G., Francomano, C.A., Puffenberger, E., Conrad, E.U., Schmale, G., Schellenberg, G., Wijsman, E., Hecht, J.T., Wells, D., and Wagner, M., Genetic heterogeneity in families with hereditary multiple exostoses, J. Am. J. Hum. Genet., 53, 71, 1993.
73. LeMerrer, M., Legeai-Mallet, L., Jeannin, P.M., Horsthemke, B., Schinzel, A., Plauchu, H., Toutain, A., Achard, F., Munnich, A., and Maroteaux, P., A gene for hereditary multiple exostoses maps to chromosome 19p, Hum. Mol. Genet., 3, 717, 1994.
74. Wu, Y.Q., Heutink, P., De Vries, B.B., Sandkuijl, L.A., Van den Ouweland, A.M., Niermeijer, M.F., Galjaard, H., Reyniers, E., Willems, P.J., and Halley, D., Assignment of a second locus for multiple exostoses to the pericentromeric region of chromosome 11, J. Hum. Mol. Genet., 3, 167, 1994.
75. Lin, X., Wei, G., Shi, Z., Dryer, L., Esko, J.D., Wells, D.E., and Matzuk, M.M., Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-Deficient Mice, Dev. Biol., 224, 299, 2000.
76. Inatani, M., Irie, F., Plump, A.S., Tessier-Lavigne, M., and Yamaguchi, Y., Mammalian brain morphogenesis and midline axon guidance require heparan sulfate, Science, 302, 1044, 2003.
77. Zak, B.M, Stickens, D., Wells, D., Evans, G., and Esko, J.D., A murine model for hereditary multiple exostoses (HME), Glycobiology, 12, 642, 2002.
78. Wise, C.A., Clines, G.A., Massa, H., Trask, B.J., and Lovett, M., Identification and localization of the gene for EXTL, a third member of the multiple exostoses gene family, Genome Res., 7, 10, 1997.
79. Wuyts, W., Van Hul, W., Hendrickx, J., Speleman, F., Wauters, J., De Boulle, K., Van Roy, N., Van Agtmael, T., Bossuyt, P., and Willems, P.J., Identification and characterization of a novel member of the EXT gene family, EXTL2, Eur. J. Hum. Genet., 5, 382, 1997.
80. Van Hul, W., Wuyts, W., Hendrickx, J., Speleman, F., Wauters, J., De Boulle, K., Van Roy, N., Bossuyt, P., and Willems, P.J., Identification of a third EXT-like gene (EXTL3) belonging to the EXT gene family, Genomics, 47, 230, 1998.
81. Saito, T., Seki, N., Yamauchi, M., Tsuji, S., Hayashi, A., Kozuma, S., and Hori, T., Structure, chromosomal location, and expression profile of EXTR1 and EXTR2, new members of the multiple exostoses gene family, Biochem. Biophys. Res. Commun., 243, 61, 1998.
82. Kitagawa, H., Shimakawa, H., and Sugahara, K., The tumor suppressor EXT-like gene EXTL2 encodes an a1,4-N-acetylhexosaminyltransferase that transfers N-acetylgalactosamine and N-acetylglucosamine to the common glycosaminoglycan-protein linkage region, J. Biol. Chem., 274, 13933, 1999.
83. Kim, B.-T., Kitagawa, H., Tamura, J., Saito, T., Kusche-Gullberg, M., Lindahl, U., and Sugahara, K., Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode a1,4-N-acetylglucosaminyltransferases that likely are involved in heparan sulfate/heparin biosynthesis, Proc. Natl. Acad. Sci. USA, 98, 7176, 2001.
84. Kobayashi, S., Akiyama, T., Nata, K., Abe, M., Tajima, M., Shervani, N.J., Unno, M., Matsuno, S., Sasaki, H., Takasawa, S., and Okamoto, H., Identification of a receptor for reg (regenerating gene) protein, a pancreatic jS-cell regeneration factor, J. Biol. Chem., 275, 10723, 2000.
85. Mizuno, K., Irie, S., and Sato, T., Overexpression of EXTL3/EXTR1 enhances NF-&B activity induced by TNF-a, Cell. Signal., 13, 125, 2001.
86. Yamada, S., Van Die, I., Van den Eijnden, D.H., Yokota, A., Kitagawa, H., and Sugahara, K., Demonstration of glycosaminoglycans in Caenorhabditis elegans, FEBS Lett., 459, 327, 1999.
87. Toyoda, H., Kinoshita-Toyoda, A., and Selleck, S.B., Structural analysis of gly-cosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfatein vivo, J. Biol. Chem., 275, 2269, 2000.
88. Toyoda, H., Kinoshita-Toyoda, A., Fox, B., and Selleck, S.B., Structural analysis of glycosaminoglycans in animals bearing mutations in sugarless, sulfateless, and tout-velu: Drosophila homologues of vertebrate genes encoding glycosaminoglycan biosynthetic enzymes, J. Biol. Chem., 275, 21856, 2000.
89. Bellaiche, Y., The, I., and Perrimon, N., Tout-velu is a Drosophila homologue of the putative tumour suppressor EXT-1 and is needed for Hh diffusion, Nature, 394, 85, 1998.
90. The, I., Bellaiche, Y., and Perrimon, N., Hedgehog movement is regulated through tout velu-dependent synthesis of a heparan sulfate proteoglycan, Mol. Cell, 4, 633, 1999.
91. Takei, Y., Ozawa, Y., Sato, M., Watanabe, A., and Tabata, T., Three Drosophila EXT genes shape morphogen gradients through synthesis of heparan sulfate proteoglycans, Development, 131, 73, 2003.
92. Kim, B.-T., Kitagawa, H., Tamura, J., Kusche-Gullberg, M., Lindahl, U., and Sugahara, K., Demonstration of a novel gene DEXT3 of Drosophila melanogaster as the essential N-acetylglucosamine transferase in the heparan sulfate biosynthesis: chain initiation and elongation, J. Biol. Chem., 277, 13659, 2002.
93. Clines, G.A., Ashley, J.A., Shah, S., and Lovett, M., The structure of the human multiple Exostoses 2 gene and characterization of homologs in mouse and Caenorhabditis elegans, Genome Res., 7, 359, 1997.
94. Kitagawa, H., Egusa, N., Tamura, J., Kusche-Gullberg, M., Lindahl, U., and Sugahara, K., rib-2, a Caenorhabditis elegans homolog of the human tumor suppressor EXT genes encodes a novel a1,4-N-acetylglucosaminyltransferase involved in the biosynthetic initiation and elongation of heparan sulfate, J. Biol. Chem., 276, 4834, 2001.
95. Morio, H., Honda, Y., Toyoda, H., Nakajima, M., Kurosawa, H., and Shirasawa, T., EXT gene family member rib-2 is essential for embryonic development and heparan sulfate biosynthesis inCaenorhabditis elegans, Biochem. Biophys. Res. Commun., 301, 317, 2003.
96. Brandan, E. and Hirschberg, C.B., Purification of rat liver N-heparan-sulfate sulfo-transferase, J. Biol. Chem., 263, 2417, 1988.
97. Pettersson, I., Kusche, M., Unger, E., Wlad, H., Nylund, L., Lindahl, U., and Kjellen, L., Biosynthesis of heparin: purification of a 110-kDa mouse mastocytoma protein required for both glucosaminyl N-deacetylation and N-sulfation. J. Biol. Chem., 266, 8044, 1991.
98. Hashimoto, Y., Orellana, A., Gil, G., and Hirschberg, C.B., Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase, J. Biol. Chem., 267, 15744, 1992.
99. Eriksson, I., Sandbäck, D., Ek, B., Lindahl, U., and Kjellen, L., cDNA cloning and sequencing of mouse mastocytoma glucosaminyl N-deacetylase/N-sulfotransferase, an enzyme involved in the biosynthesis of heparin, J. Biol. Chem., 269, 10438, 1994.
100. Aikawa, J. and Esko, J.D., Molecular cloning and expression of a third member of the heparan sulfate/heparin GlcNAc N-deacetylase/N-sulfotransferase family, J. Biol. Chem., 274, 2690, 1999.
101. Aikawa, J., Grobe, K., Tsujimoto, M., and Esko, J.D., Multiple isozymes of heparan sulfate/heparin GlcNAc N-Deacetylase/GlcN N-sulfotransferase: structure and activity of the fourth member, NDST4, J. Biol. Chem., 276, 5876, 2001.
102. Fan, G., Xiao, L., Cheng, L., Wang, X., Sun, B., and Hu, G., Targeted disruption of NDST-1 gene leads to pulmonary hypoplasia and neonatal respiratory distress in mice, FEBS Lett., 467, 7, 2000.
103. Ringvall, M., Ledin, J., Holmborn, K., Van Kuppevelt, T., Ellin, F., Eriksson, I., Olofsson, A.-M., Kjellen, L., Forsberg, E., Olofsson, A.-M., Kjellen, L., and Forsberg, E. Defective heparan sulfate biosynthesis and neonatal lethality in mice lacking N-deacetylase/N-sulfotransferase-1, J. Biol. Chem., 275, 25926, 2000.
104. Grobe, K., Ledin, J., Ringvall, M., Holmborn, K., Forsberg, E., Esko, J.D., and Kjellen, L., Heparan sulfate and development: differential roles of the N-acetylglu-cosamine N-deacetylase/N-sulfotransferase isozymes, Biochim. Biophys. Acta, 1573, 209, 2002.
105. Thomas, K.R. and Capecchi, M.R., Targeted disruption of the murine int-1 protooncogene resulting in severe abnormalities in midbrain and cerebellar development, Nature, 346, 847, 1990.
106. McMahon, A.P. and Bradley, A., The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain, Cell, 62, 1073, 1990.
107. Chiang, C., Litingtung, Y., Lee, E., Young, K.E., Corden, J.L., Westphal, H., and Beachy, P.A., Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function, Nature, 383, 407, 1996.
108. Bachiller, D., Klingensmith, J., Kemp, C., Belo, J.A., Anderson, R.M., May, S.R., McMahon, J.A., McMahon, A.P., Harland, R.M., Rossant, J., and De Robertis, E.M., The organizer factors Chordin and Noggin are required for mouse forebrain development, Nature, 403, 658, 2000.
109. 2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective myotubes, J. Cell Sci., 116, 2187, 2003.
110. Humphries, D.E., Wong, G.W., Friend, D.S., Gurish, M.F., Qiu, W.-T., Huang, C., Sharpe, A.H., and Stevens, R.L., Heparin is essential for the storage of specific granule proteases in mast cells, Nature, 400, 769, 1999.
111. Forsberg, E., Pejler, G., Ringvall, M., Lunderius, C., Tomasini-Johansson, B., KuscheGullberg, M., Eriksson, I., Ledin, J., Hellman, L., and Kjellen, L., Abnormal mast cells in mice deficient in a heparin-synthesizing enzyme, Nature, 400, 773, 1999.
112. Campbell, P., Hannesson, H.H., Sandback, D., Roden, L., Lindahl, U., and Li, J.-P., Biosynthesis of heparin/heparan sulfate: Purification of the D-glucuronyl C-5 epimerase from bovine liver, J. Biol. Chem., 269, 26953, 1994.
113. Hagner-McWhirter, A., Li, J.-P., Oscarson, S., and Lindahl, U., Irreversible glu-curonyl C5-epimerization in the biosynthesis of heparan sulfate, J. Biol. Chem., 279, 1463, 2004.
114. Li, J.-P., Hagner-McWhirter, A., Kjellen, L., Palgi, J., Jalkanen, M., and Lindahl, U., Biosynthesis of heparin/heparan sulfate: cDNA cloning and expression of D-Glucuronyl C5-epimerase from bovine lung, J. Biol. Chem., 272, 28158, 1997.
115. Li, J.-P., Gong, F., Darwish, K.E., Jalkanen, M., and Lindahl, U., Characterization of the D-glucuronyl C5-epimerase involved in the biosynthesis of heparin and heparan sulfate, J. Biol. Chem., 276, 20069, 2001.
116. Crawford, B.E., Olson, S.K., Esko, J.D., and Pinhal, M.A.S., Cloning, golgi localization, and enzyme activity of the full-length heparin/heparan sulfate-glucuronic acid C5-epimerase, J. Biol. Chem., 276, 21538, 2001.
117. Jacobsson, I., Backstrom, G., Hook, M., Lindahl, U., Feingold, D.S., Malmstrom, A., and Roden, L., Biosynthesis of heparin: assay and properties of the microsomal uronosyl C-5 epimerase, J. Biol. Chem., 254, 2975, 1979.
118. Casu, B., Petitou, M., Provasoli, M., and Sinay, P., Conformational flexibility: a new concept for explaining binding and biological properties of iduronic acid-containing glycosaminoglycans, Trends Biochem. Sci., 13, 221, 1988.
119. Li, J.-P., Gong, F., Hagner-McWhirter, A., Forsberg, E., Abrink, M., Kisilevsky, R., Zhang, X., and Lindahl, U., Targeted disruption of a murine glucuronyl C5-epimerase gene results in heparan sulfate lacking L-iduronic acid and in neonatal lethality, J. Biol. Chem., 278, 28363, 2003.
120. Bullock, S.L., Fletcher, J.M., Beddington, R.S.P., and Wilson, V.A., Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase, Genes Dev., 12, 1894, 1998.
121. Kobayashi, M., Habuchi, H., Habuchi, O., Saito, M., and Kimata, K., Purification and characterization of heparan sulfate 2-sulfotransferase from cultured chinese hamster ovary cells, J. Biol. Chem., 271, 7645, 1996.
122. Kobayashi, M., Habuchi, H., Yoneda, M., Habuchi, O., and Kimata, K., Molecular cloning and expression of chinese hamster ovary cell heparan-sulfate 2-sulfotrans-ferase, J. Biol. Chem., 272, 13980, 1997.
123. Bai, X. and Esko, J.D., An animal cell mutant defective in heparan sulfate hexuronic acid 2-0-sulfation, J. Biol. Chem., 271, 17711, 1996.
124. Pinhal, M.A.S., Smith, B., Olson, S., Aikawa, J., Kimata, K., and Esko, J.D., Enzyme interactions in heparan sulfate biosynthesis: Uronosyl 5-epimerase and 2-0-sulfo-transferase interact in vivo, Proc. Natl. Acad. Sci. USA, 98, 12984, 2001.
125. McLaughlin, D., Karlsson, F., Tian, N., Pratt, T., Bullock, S.L., Wilson, V.A., Price, D.J., and Mason, J.O., Specific modification of heparan sulphate is required for normal cerebral cortical development, Mech. Dev., 120, 1481, 2003.
126. Merry, C.L.R., Bullock, S.L., Swan, D.C., Backen, A.C., Lyon, M., Beddington, R.S.P., Wilson, V.A., and Gallagher, J.T., The molecular phenotype of heparan sulfate in the Hs2stmutant mouse, J. Biol. Chem., 276, 35429, 2001.
127. Sen, J., Golts, J.S., Stevens, L., and Stein, D., Spatially restricted expression of pipe in the Drosophila egg chamber defines embryonic dorsal-ventral polarity, Cell, 95, 471, 1998.
128. Merrill, C., Bayraktaroglu, L., Kusano, A., and Ganetzky, B., Truncated RanGAP encoded by the Segregation Distorter locus ofDrosophila, Science, 283, 1742, 1999.
129. Habuchi, H., Habuchi, O., and Kimata, K. J., Purification and characterization of heparan sulfate 6-sulfotransferase from the culture medium of chinese Hamster ovary cells, Biol. Chem., 270, 4172, 1995.
130. Habuchi, H., Kobayashi, M., and Kimata, K.J., Molecular characterization and expression of heparan-sulfate 6-Sulfotransferase: complete cDNA cloning in human and partial cloning in chinese hamster ovary cells, Biol. Chem., 273, 9208, 1998.
131. Habuchi, H., Tanaka, M., Habuchi, O., Yoshida, K., Suzuki, H., Ban, K., and Kimata, K.J., The occurrence of three isoforms of heparan sulfate 6-0-sulfotransferase having different specificities for hexuronic acid adjacent to the targeted N-sulfoglucosamine, Biol. Chem.,275, 2859, 2000.
132. Habuchi, H., Miyake, G., Nogami, K., Kuroiwa, A., Matsuda, Y., Kusche-Gullberg, M., Habuchi, O., Tanaka, M., and Kimata, K., Biosynthesis of heparan sulphate with diverse structures and functions: two alternatively spliced forms of human heparan sulphate 6-0-sulphotransferase-2 having different expression patterns and properties, Biochem. J., 371, 131, 2003.
133. Smeds, E., Habuchi, H., Do, A.-T., Hjertson, E., Grundberg, H., Kimata, K., Lindahl, U., and Kuche-Gullberg, M., Substrate specificities of mouse heparan sulphate glu-cosaminyl 6-0-sulphotransferases, Biochem. J., 372, 371, 2003.
134. Kamimura, K., Fujise, M., Villa, F., Izumi, S., Habuchi, H., Kimata, K., and Nakato, K.J., Drosophila heparan sulfate 6-0-sulfotransferase (dHS6ST) gene: structure, expression, and function in the formation of the tracheal system, Biol. Chem., 276, 17014, 2001.
135. Lindahl, U., Backstrom, G., Thunberg, L., and Leder, I. G., Evidence for a 3-0-sul-fated D-glucosamine residue in the antithrombin-binding sequence of heparin, Proc. Natl. Acad. Sci. USA, 77, 6551, 1980.
136. Liu, J., Shworak, N.W., Fritze, L.M.S., Edelberg, J.M., and Rosenberg, R.D., Purification of heparan sulfate D-glucosaminyl 3-0-sulfotransferase, J. Biol. Chem., 271, 27072, 1996.
137. Shworak, N.W., Liu, J., Fritze, L.M.S., Schwartz, J.J., Zhang, L., Logeart, D., and Rosenberg, R.D., Molecular cloning and expression of mouse and human cDNAs encoding heparan sulfate D-glucosaminyl 3-0-sulfotransferase, J. Biol. Chem., 272, 28008, 1997.
138. Shworak, N.W., Liu, J., Petros, L.M., Zhang, L., Kobayashi, M., Copeland, N.G., Jenkins, N.A., and Rosenberg, R.D., Multiple isoforms of heparan sulfate D-glucosaminyl 3-O-sulfotransferase: isolation, characterization, and expression of human cDNAs and identification of distinct genomic loci, J. Biol. Chem., 274, 5170, 1999.
139. Liu, J., Shworak, N.W., Sinay, P., Schwartz, J.J., Zhang, L., Fritze, L.M.S., and Rosenberg, R.D., Expression of heparan sulfate D-glucosaminyl 3-O-sulfotransferase isoforms reveals novel substrate specificities, J. Biol. Chem., 274, 5185, 1999.
140. Xia, G., Chen, J., Tiwari, V., Ju, W., Li, J. -P., Malmström, A., Shukla, D., and Liu, J., Heparan sulfate 3-O-sulfotransferase isoform 5 generates both an antithrombin-binding site and an entry receptor for herpes simplex virus, type 1, J. Biol. Chem., 277, 37912, 2002.
141. Shukla, D., Liu, J., Blaiklock, P., Shworak, N.W., Bai, X., Esko, J.D., Cohen, G.H., Eisenberg, R.J., Rosenberg, R.D., and Spear, P.G., A novel role for 3-O-sulfated heparan sulfate in herpes simplex virus 1 entry, Cell, 99, 13, 1999.
142. McKeehan, W.L., Wu, X., and Kan, M., Requirement for anticoagulant heparan sulfate in the fibroblast growth factor receptor complex, J. Biol. Chem., 274, 21511, 1999.
143. Ye, S., Luo, Y., Lu, W., Jones, R.B., Linhardt, R.J., Capila, I., Toida, T., Kan, M., Pelletier, H., and McKeehan, W.L., Structural basis for interaction of FGF-1, FGF-2, and FGF-7 with different heparan sulfate motifs, Biochemistry, 40, 14429, 2001.
144. HajMohammadi, S., Enjoji, K., Princivalle, M., Christi, P., Lech, M., Beeler, D., Rayburn, H., Schwartz, J.J., Barzeger, S., De Agostini, A.I., Post, M.J., Rosenberg, R.D., and Shworak, N.W., Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis, J. Clin. Invest., 111, 989, 2003.
145. Hwang, H.-Y. and 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 Caenorhabditis elegans vulval morphogenesis and embryonic development, Proc. Natl. Acad. Sci. USA, 99, 14218, 2002.
146. Hwang, H.-Y., Olson, S.K., Brown, J.R., Esko, L.D., and Horvitz, H.R., The Caenorhabditis elegans genes sqv-2 and sqv-6, which are required for vulval morphogenesis, encode glycosaminoglycan galactosyltransferase II and xylosyltrans-ferase, J. Biol. Chem., 278, 11735, 2003.
147. Hwang, H.-Y. and Horvitz, H.R., 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, 2002.
148. Merz, D.C., Alves, G., Kawano, T., Zheng, H., and Culotti, J.G., UNC-52/Perlecan affects gonadal leader cell migrations in C. elegans hermaphrodites through alterations in growth factor signaling, Dev. Biol., 256, 174, 2003.
149. Rogalski, T.M., Mullen, G.P., Bush, J.A., Gilchrist, E.J., and Moerman, D.G., UNC-52/perlecan isoform diversity and function in Caenorhabditis elegans, Biochem. Soc. Trans, 29, 171, 2001.
150. Bülow, H.E., Berry, K.L., Topper, L.H., Peles, E., and Hobert, O., Heparan sulfate proteoglycan-dependent induction of axon branching and axon misrouting by the Kallmann syndrome genekal-1, Proc. Natl. Acad. Sci., USA, 99, 6346, 2002.
151. Wilson, I.B.H., Functional characterization of Drosophila melanogaster peptide O-Xylosyltransferase, the key enzyme for proteoglycan chain initiation and member of the core 2/I N-acetylglucosaminyltransferase family, J. Biol. Chem., 277, 21207, 2002.
152. Takemae, H., Ueda, R., Okubo, R., Nakato, H., Izumi, S., Saigo, K., and Nishihara, S., Proteoglycan UDP-galactose: ß-xylose jö1,4-galactosyltransferase I is essential for viability in Drosophila melanogaster, J. Biol. Chem., 278, 15571, 2003.
153. Nakato, H., Futch, T.A., and Selleck, S.B., The division abnormally delayed (dally) gene: a putative integral membrane proteoglycan required for cell division patterning during postembryonic development of the nervous system inDrosophila, Development, 121, 3687, 1995.
154. Jackson, S.M., Nakato, H., Sugiura, M., Jannuzi, A., Oakes, R., Kaluza, V., Golden, C., and Selleck, S.B., dally, a Drosophila glypican, controls cellular responses to the TGF-jö-related morphogen, Dpp, Development, 124, 4113, 1997.
155. Tsuda, M., Kamimura, K., Nakato, H., Archer, M., Staatz, W., Fox, B., Humphrey, M., Olson, S., Futch, T., Kaluza, V., Siegfried, E., Stam, L., and Selleck, S.B., The cell-surface proteoglycan Dally regulates Wingless signalling inDrosophila, Nature, 400, 276, 1999.
156. Fujise, M., Takeo, S., Kamimura, K., Matsuo, T., Aigaki, T., Izumi, S., and Nakato, H., Dally regulates Dpp morphogen gradient formation in the Drosophila wing, Development, 130, 1515, 2003.
157. Han, C., Belenkaya, T.Y., Wang, B., and Lin, X., Drosophila glypicans control the cell-to-cell movement of Hedgehog by a dynamin-independent process, Development, 131, 601, 2004.
158. Baeg, G.-H., Lin, X., Khare, N., Baumgartner, S., and Perrimon, N., Heparan sulfate proteoglycans are critical for the organization of the extracellular distribution of Wingless, Development, 128, 87, 2001.
159. Desbordes, S.C. and Sanson, B., The glypican Dally-like is required for Hedgehog signalling in the embryonic epidermis ofDrosophila, Development, 130, 6245, 2003.
160. Spring, J., Paine-Saunders, S.E., Hynes, R.O., and Bernfield, M., Drosophila synde-can: conservation of a cell-surface heparan sulfate proteoglycan, Proc. Natl. Acad. Sci. USA., 91, 3334, 1994.
161. Voigt, A., Pflanz, R., Schäfer, U., and Jäckle, H., Perlecan participates in proliferation activation of quiescent Drosophila neuroblasts, Dev. Dyn., 224, 403, 2002.
162. Golling, G., Amsterdam, A., Sun, Z., Antonelli, M., Maldonado, E., Chen, W., Burgess, S., Haldi, M., Artzt, K., Farrington, S., Lin, S.-Y., Nissen, R.M., and Hopkins, N., Insertional mutagenesis in zebrafish rapidly identifies genes essential for early vertebrate development, Nat. Genet., 31, 135, 2002.
163. Bink, R.J., Habuchi, H., Lele, Z., Dolk, E., Joore, J., Rauch, G.-J., Geisler, R., Wilson, S.W., Den Hertog, J., Kimata, K., and Zivkovic, D., Heparan sulfate 6-O-sulfotrans-ferase is Essential for muscle development in zebrafish, J. Biol. Chem., 278, 31118, 2003.
164. Topczewski, J., Sepich, D.S., Myers, D.C., Walker, C., Amores, A., Lele, Z., Hammerschmidt, M., Postlethwait, J., and Solnica-Krezel, L., The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension, Dev. Cell, 1, 251, 2001.
165. Chen, E., Hermanson, S., and Ekker, S.C., Syndecan-2 is essential for angiogenic sprouting during zebrafish development, Blood, 103, 1710, 2004.
166. Watanabe, H., Kimata, K., Line, S., Strong, D., Gao, L.Y., Kozak, C.A., and Yamada, Y., Mouse cartilage matrix deficiency (cmd) caused by a 7 bp deletion in the aggrecan gene, Nat. Genet., 7, 154, 1994.
167. Mjaatvedt, C.H., Yamamura, H., Capehart, A.A., Turner, D., and Markwald, R.R., The Cspg2 gene, disrupted in the hdf mutant, is required for right cardiac chamber and endocardial cushion formation, Dev. Biol., 202, 56, 1998.
168. Alexander, C.M., Reichsman, F., Hinkes, M.T., Lincecum, J., Becker, K.A., Cumberledge, S., and Bernfield, M., Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice, Nat. Genet., 25, 329, 2000.
169. Bernfield, M., Gotte, M., Park, P.W., Reizes, O., Fitzgerald, M.L., Lincecum, J., and Zako, M., Functions of cell surface heparan sulfate proteoglycans, Annu. Rev. Biochem., 68, 729, 1999.
170. Reizes, O., Lincecum, J., Wang, Z., Goldberger, O., Huang, L., Kaksonen, M., Ahima, R., Hinkes, M.T., Barsh, G.S., Rauvala, H., and Bernfield, M., Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3, Cell, 106, 105, 2001.
171. Ishiguro, K., Kadomatsu, K., Kojima, T., Muramatsu, H., Tsuzuki, S., Nakamura, E., Kusugami, K., Saito, H., and Muramatsu, T., Syndecan-4 deficiency impairs focal adhesion formation only under restricted conditions, J. Biol. Chem., 275, 5249, 2000.
172. Perrimon, N. and Bernfield, M., Specificities of heparan sulphate proteoglycans in developmental processes, Nature, 404, 725, 2000.
173. Cano-Gauci, D.F., Song, H.H., Yang, H., McKerlie, C., Choo, B., Shi, W., Pullano, R., Piscione, T.D., Grisaru, S., Soon, S., Sedlackova, L., Tanswell, A.K., Mak, T.W., Yeger, H., Lockwood, G.A., Rosenblum, N.D., and Filmus, J., Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of simpson-golabi-behmel syndrome, J. Cell Biol., 146, 255, 1999.
174. Gautam, M., Noakes, P.G., Moscoso, L., Rupp, F., Scheller, R.H., Merlie, J.P., and Sanes, J.R., Defective neuromuscular synaptogenesis in agrin-deficient mutant mice, Cell, 85, 525, 1996.
175. Aikawa-Hirasawa, E., Watanabe, H., Takami, H., Hassell, J.R., and Yamada, Y., Perlecan is essential for cartilage and cephalic development, Nat. Genet., 23, 354, 1999.
176. Costell, M., Gustafsson, E., Aszodi, A., Morgelin, M., Bloch, W., Hunziker, E., Addicks, K., Timpl, R., and Fassler, R., Perlecan maintains the integrity of cartilage and some basement membranes, J. Cell Biol., 147, 1109, 1999.
177. Danielson, K.G., Baribault, H., Holmes, D.F., Graham, H., Kadler, K.E., and Iozzo, R.V., Targeted disruption of decorin leads to abnormal collagen fibril Morphology and skin fragility, J. Cell Biol., 136, 729, 1997.
178. Xu, T., Bianco, P., Fisher, L.W., Longenecker, G., Smith, E., Goldstein, S., Bonadio, J., Boskey, A., Heegaard, A. -M., Sommer, B., Satomura, K., Dominguez, P., Zhao, C., Kulkarni, A.B., Robey, P.G., and Young, M.F., Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice, Nat. Genet., 20, 78, 1998.
179. Zhou, X.-H., Brakebusch, C., Matthies, H., Oohashi, T., Hirsch, E., Moser, M., Krug, M., Seidenbecher, C.I., Boeckers, T.M., Rauch, U., Buettner, R., Gundelfinger, E.D., and Fassler, R., Neurocan is dispensable for brain development, Mol. Cell Biol., 21, 5970, 2001.
180. Fujikawa, A., Shirasaka, D., Yamamoto, S., Ota, H., Yahiro, K., Fukuda, M., Shintani, T., Wada, A., Aoyama, N., Hirayama, T., Fukumachi, H., and Noda, M., Mice deficient in protein tyrosine phosphatase receptor type Z are resistant to gastric ulcer induction by VacA ofHelicobacter pylori, Nat. Genet., 33, 375, 2003.
181. Healy, A.M., Rayburn, H.B., Rosenberg, R.D., and Weiler, H., Absence of the bloodclotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system, Proc. Natl. Acad. Sci. USA, 92, 850, 1995.
182. Zak, B.M., Crawford, B.E., and Esko, J.D., Hereditary multiple exostoses and heparan sulfate polymerization, Biochim. Biophys. Acta, 1573, 346, 2002.
183. Sugahara, K. and Kitagawa, H., Heparin and heparan sulfate biosynthesis, IUBMB Life, 54, 163, 2002.
184. Sugahara, K., Yamashina, I., de Waard, P., Van Halbeek, H and Vliegenthart, J.F.G., Structural studies on sulfated glycopeptides from the carbohydrate- protein linkage region of chondroitin 4-sulfate proteoglycans of swarm rat chondrosarcoma: demonstration of the structure GAL(4-O-sulfate) j8l-3Galj8l-4XYL y81-O-ser, J. Biol. Chem., 263, 10168, 1988.
185. Sugahara, K., Ohi, Y., Harada, T., de Waard, P., and Vliegenthart, J.F.G., Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage: I. Six compounds containing 0 or 1 sulfate and/or phosphate residues, J. Biol. Chem., 267, 6027, 1992.
186. de Waard, P., Vliegenthart, J.F.G., Harada, T., and Sugahara, K., Structural studies on sulfated oligosaccharides derived from the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage: II. Seven compounds containing 2 or 3 sulfate residues, J. Biol. Chem., 267, 6036 1992.