Recent advances in the structural biology of chondroitin sulfate and dermatan sulfate
Abstract
Recent glycobiology studies have suggested fundamental biological functions for chondroitin, chondroitin sulfate and dermatan sulfate, which are widely distributed as glycosaminoglycan sidechains of proteoglycans in the extracellular matrix and at cell surfaces. They have been implicated in the signaling functions of various heparin-binding growth factors and chemokines, and play critical roles in the development of the central nervous system. They also function as receptors for various pathogens. These functions are closely associated with the sulfation patterns of the glycosaminoglycan chains. Surprisingly, nonsulfated chondroitin is indispensable in the morphogenesis and cell division of Caenorhabditis elegans, as revealed by RNA interference experiments of the recently cloned chondroitin synthase gene and by the analysis of mutants of squashed vulva genes.
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Chondroitinase ABC promotes functional recovery after spinal cord injury
Bradbury, E. J., Moon, L. D. F., Popat, R. J., King, V. R., Bennett, G. S., Patel, P. N., Fawcett, J. W., & McMahon, S. B. (2002) · Nature · doi:10.1038/416636a · Cited by 2,357 · see citing works
Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex
Pizzorusso, T., Medini, P., Berardi, N., Chierzi, S., Fawcett, J. W., & Maffei, L. (2002) · Science · doi:10.1126/science.1072699 · Cited by 1,679 · see citing works
Specificities of heparan sulphate proteoglycans in developmental processes
Perrimon, N., & Bernfield, M. R. (2000) · Nature · doi:10.1038/35008000 · Cited by 713 · see citing works
Proteoglycans in the Developing Brain: New Conceptual Insights for Old Proteins
Bandtlow, C. E., & Zimmermann, D. R. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.4.1267 · Cited by 632 · see citing works
Moon, L. D. F., Asher, R. A., Rhodes, K. E., & Fawcett, J. W. (2001) · Nature Neuroscience · doi:10.1038/87415 · Cited by 563 · see citing works
Dermatan sulfate: new functions from an old glycosaminoglycan
Trowbridge, J. M., & Gallo, R. L. (2002) · Glycobiology · doi:10.1093/glycob/cwf066 · Cited by 459 · see citing works
Chapter 22 Chondroitin sulphate proteoglycans in the CNS injury response
Morgenstern, D. A., Asher, R. A., & Fawcett, J. W. (2002) · Progress in brain research · doi:10.1016/s0079-6123(02)37024-9 · Cited by 419 · see citing works
Meng, K., Rodríguez‐Peña, A., Dimitrov, T., Chen, W., Yamin, M., Noda, M., & Deuel, T. F. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.020487997 · Cited by 414 · see citing works
Stoica, G. E., Kuo, A. H., Powers, C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205749200 · Cited by 359 · see citing works
Deepa, S. S., Umehara, Y., Higashiyama, S., Itoh, N., & Sugahara, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207105200 · Cited by 332 · see citing works
Self-citationBiosynthesis of Chondroitin/Dermatan Sulfate
Silbert, J. E., & Sugumaran, G. (2002) · IUBMB Life · doi:10.1080/15216540214923 · Cited by 330 · see citing works
Margolis, R. K., & Margolis, R. U. (1993) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923587 · Cited by 265 · see citing works
Brakebusch, C., Seidenbecher, C. I., Asztely, F., Rauch, U., Matthies, H., Meyer, H., Krug, M., Böckers, T. M., Zhou, X., Kreutz, M. R., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.21.7417-7427.2002 · Cited by 264 · see citing works
Chondroitin proteoglycans are involved in cell division of Caenorhabditis elegans
Mizuguchi, S., Uyama, T., Kitagawa, H., Nomura, K. H., Dejima, K., Gengyo‐Ando, K., Mitani, S., Sugahara, K., & Nomura, K. (2003) · Nature · doi:10.1038/nature01635 · Cited by 261 · see citing works
Self-citationHeparin and Heparan Sulfate Biosynthesis
Sugahara, K., & Kitagawa, H. (2002) · IUBMB Life · doi:10.1080/15216540214928 · Cited by 260 · see citing works
Self-citationBéchard, D., Gentina, T., Delehedde, M., Scherpereel, A., Lyon, M., Aumercier, M., Vazeux, R., Richet, C., Degand, P., Jude, B., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m108395200 · Cited by 241 · see citing works
Kawashima, H., Atarashi, K., Hirose, M., Hirose, J., Yamada, S., Sugahara, K., & Miyasaka, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200396200 · Cited by 241 · see citing works
Self-citationBukalo, O., Schachner, M., & Dityatev, A. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00082-3 · Cited by 236 · see citing works
Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis
Hwang, H., Olson, S. K., Esko, J. D., & Horvitz, H. R. (2003) · Nature · doi:10.1038/nature01634 · Cited by 207 · see citing works
Molecular Cloning and Expression of a Human Chondroitin Synthase
Kitagawa, H., Uyama, T., & Sugahara, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106871200 · Cited by 206 · see citing works
Self-citationNeurocan Is Dispensable for Brain Development
Zhou, X.-H., Brakebusch, C., Matthies, H., Oohashi, T., Hirsch, E., Moser, M., Krug, M., Seidenbecher, C. I., Boeckers, T. M., Rauch, U., et al. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.17.5970-5978.2001 · Cited by 206 · see citing works
Clement, A. M., Nadanaka, S., Masayama, K., Mandl, C., Sugahara, K., & Faissner, A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.43.28444 · Cited by 175 · see citing works
Self-citationKitagawa, H., Izumikawa, T., Uyama, T., & Sugahara, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302493200 · Cited by 169 · see citing works
Self-citationMolecular Interactions of Neural Chondroitin Sulfate Proteoglycans in the Brain Development
Oohira, A., Matsui, F., Tokita, Y., Yamauchi, S., & Aono, S. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1598 · Cited by 161 · see citing works
Heparin-binding proteins HB-GAM (pleiotrophin) and amphoterin in the regulation of cell motility
Rauvala, H., Huttunen, H. J., Fages, C., Kaksonen, M., Kinnunen, T. K., Imai, S., Raulo, E., & Kilpeläinen, I. (2000) · Matrix Biology · doi:10.1016/s0945-053x(00)00084-6 · Cited by 143 · see citing works
Okajima, T., Yoshida, K., Kondo, T., & Furukawa, K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.22915 · Cited by 143 · see citing works
Ueoka, C., Kaneda, N., Okazaki, I., Nadanaka, S., Muramatsu, T., & Sugahara, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002538200 · Cited by 136 · see citing works
Self-citationChondrodysplasias due to proteoglycan defects
Schwartz, N. B., & Domowicz, M. S. (2002) · Glycobiology · doi:10.1093/glycob/12.4.57r · Cited by 129 · see citing works
Molecular Cloning and Expression of Human ChondroitinN-Acetylgalactosaminyltransferase
Uyama, T., Kitagawa, H., Tamura, J., & Sugahara, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111434200 · Cited by 128 · see citing works
Self-citationsqv mutants of Caenorhabditis elegans are defective in vulval epithelial invagination
Herman, T. G., Hartwieg, E. A., & Horvitz, H. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.3.968 · Cited by 128 · see citing works
Berninsone, P. M., Hwang, H., Zemtseva, I. S., Horvitz, H. R., & Hirschberg, C. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.061593098 · Cited by 124 · see citing works
Hikino, M., Mikami, T., Faissner, A., Vilela-Silva, A.-C. E. S., Pavão, M. S. G., & Sugahara, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m308169200 · Cited by 124 · see citing works
Self-citationFischer, J. R., Parveen, N., Magoun, L., & Leong, J. M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1231043100 · Cited by 122 · see citing works
Bulik, D. A., Wei, G., Toyoda, H., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.20.10838 · Cited by 120 · see citing works
Uyama, T., Kitagawa, H., Tanaka, J., Tamura, J., Ogawa, T., & Sugahara, K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209446200 · Cited by 115 · see citing works
Self-citationNo Obvious Abnormality in Mice Deficient in Receptor Protein Tyrosine Phosphatase β
Harroch, S., Palmeri, M., Rosenbluth, J. M., Custer, A., Okigaki, M., Shrager, P., Blum, M., Buxbaum, J. D., & Schlessinger, J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.20.7706-7715.2000 · Cited by 115 · see citing works
Bai, X., Wei, G., Sinha, A., & Esko, J. D. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.19.13017 · Cited by 108 · see citing works
Kawachi, H., Fujikawa, A., Maeda, N., & Noda, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.041608698 · Cited by 107 · see citing works
Demonstration of glycosaminoglycans in Caenorhabditis elegans
Yamada, S., van Die, I., EIJNDEN, D. H. V. D., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01286-7 · Cited by 106 · see citing works
Dermatan Sulfate Binds and Potentiates Activity of Keratinocyte Growth Factor (FGF-7)
Trowbridge, J. M., Rudisill, J. A., Ron, D., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204959200 · Cited by 104 · see citing works
Tanaka, M., Maeda, N., Noda, M., et al. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-07-02804.2003 · Cited by 96 · see citing works
Maeda, N., He, J., Yajima, Y., Mikami, T., Sugahara, K., & Yabe, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305530200 · Cited by 96 · see citing works
Self-citationEnhanced bacterial virulence through exploitation of host glycosaminoglycans
Menozzi, F. D., Pethe, K., Bifani, P. J., et al. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02841.x · Cited by 96 · see citing works
Garwood, J., Heck, N., Reichardt, F., & Faissner, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211721200 · Cited by 94 · see citing works
Sugahara, K., & Yamada, S. (2000) · Trends in Glycoscience and Glycotechnology · doi:10.4052/tigg.12.321 · Cited by 89 · see citing works
Self-citationFrick, I.-M., Schmidtchen, A., & Sjöbring, U. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03600.x · Cited by 88 · see citing works
Hwang, H., Olson, S. K., Brown, J. R., Esko, J. D., & Horvitz, H. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c200518200 · Cited by 86 · see citing works
Uchimura, K., Kadomatsu, K., Nishimura, H., Muramatsu, H., Nakamura, E., Kurosawa, N., Habuchi, O., El-Fasakhany, F. M., Yoshikai, Y., & Muramatsu, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m104719200 · Cited by 86 · see citing works
Parveen, N., Caimano, M. J., Radolf, J. D., et al. (2003) · Molecular Microbiology · doi:10.1046/j.1365-2958.2003.03388.x · Cited by 85 · see citing works
Hwang, H., & Horvitz, H. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172522199 · Cited by 85 · see citing works
Glycosaminoglycan structures required for strong binding to midkine, a heparin-binding growth factor
Zou, P. (2002) · Glycobiology · doi:10.1093/glycob/cwg001 · Cited by 78 · see citing works
Mårdberg, K., Trybala, E., Tufaro, F., et al. (2002) · Journal of General Virology · doi:10.1099/0022-1317-83-2-291 · Cited by 78 · see citing works
Gotoh, M., Yada, T., Sato, T., Akashima, T., Iwasaki, H., Mochizuki, H., Inaba, N., Togayachi, A., Kudo, T., Watanabe, H., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202601200 · Cited by 77 · see citing works
Lyon, M., Deakin, J. A., & Gallagher, J. T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107506200 · Cited by 76 · see citing works
Hwang, H., & Horvitz, H. R. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172522499 · Cited by 71 · see citing works
Achur, R. N., Valiyaveettil, M., & Gowda, D. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211015200 · Cited by 67 · see citing works
Chai, W., Beeson, J. G., & Lawson, A. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111401200 · Cited by 63 · see citing works
Garwood, J., Rigato, F., Heck, N., & Faissner, A. (2001) · PubMed · Cited by 57 · see citing works
Tsuchida, K., Shioi, J., Yamada, S., Boghosian, G., Wu, A., Cai, H., Sugahara, K., & Robakis, N. K. R. K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105818200 · Cited by 55 · see citing works
Self-citationGamain, B., Gratepanche, S., Miller, L. H., & Baruch, D. I. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152321599 · Cited by 55 · see citing works
Neuronal polarity: Giving neurons heads and tails
Prochiantz, A. (1995) · Neuron · doi:10.1016/0896-6273(95)90164-7 · Cited by 52 · see citing works
Holland, S., Peles, E., Pawson, T., & Schlessinger, J. (1998) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(98)80015-9 · Cited by 26 · see citing works
Roles of Proteoglycans in Reception of the Midkine Signal.
Muramatsu, T. (2001) · Trends in Glycoscience and Glycotechnology · doi:10.4052/tigg.13.563 · Cited by 11 · see citing works
Ichijo, H. (2003) · Connective tissue · Cited by 7 · see citing works
Maeda, N. (2003) · Connective tissue · Cited by 4 · see citing works
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- Authors
- Sugahara, K., Mikami, T., Uyama, T., Mizuguchi, S., Nomura, K., & Kitagawa, H.
- Affiliations
- Kobe Pharmaceutical University (JP)
- Kyushu University (JP)
- Corresponding author
- Sugahara, Kazuyuki
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 2003-10
- Volume
- 13
- Issue
- 5
- Pages
- 612-620
- ISSN
- 0959-440X (ISSN-L)
- OpenAlex
- W2000460436
- Cited by
- 694
- References
- 65
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 14 · 2023: 27 · 2022: 35 · 2021: 41 · 2020: 35 · 2019: 20 · 2018: 24 · 2017: 32 · 2016: 32 · 2015: 39 · 2014: 34 · 2013: 36 · 2012: 38
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Private School Promotion Foundation
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Polysaccharides and Plant Cell Walls
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Keywords
- chondroitin sulfate, dermatan sulfate, chondroitin, glycosaminoglycans, proteoglycans, extracellular matrix, sulfation patterns, heparin-binding growth factors, chemokines, central nervous system development, pathogen receptors, Caenorhabditis elegans, cell division, morphogenesis
- MeSH terms
- Animals, Brain, Cell Division, Chondroitin Sulfates, Dermatan Sulfate, Growth Substances, Heparan Sulfate, Morphogenesis, Nerve Regeneration, Neurons, Structure-Activity Relationship, Signal Transduction, Neurites, Caenorhabditis elegans
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