Neuronal axons and their growth cones recognize molecular guidance cues within the local environment, forming axonal pathways to produce precise neuronal networks during nervous system development. Chondroitin sulfates (CS), carbohydrate chains on chondroitin sulfate proteoglycans, exhibit great structural diversity and exert various influences on axons and growth cones as guidance cues or their modulators; however, the relationship between their structural diversity and function in axonal guidance is not well known. To uncover the roles of CS in axonal guidance, artificially modified hybrid molecules: CS derivatives of biotinylated CS and lipid-derivatized CS, were used. The experiments with biotinylated CS suggest that the growing axons act on their environment, modifying CS, and rendering it more favorable for their growth. The experiments with lipid-derivatized CS demonstrated that growth cones distinguish types of CS with different unit contents and are likely to discriminate the structural diversity of CS. The application of CS derivatives is useful in uncovering axon–environment interaction and structure–function relationship of CS directly.
References
[1]
Kolodkin, A.L.; Tessier-Lavigne, M. Mechanisms and molecules of neuronal wiring: A primer. Cold Spring Harb. Perspect. Biol. 2011, 3, a001727, doi:10.1101/cshperspect.a001727.
[2]
Maeda, N.; Ishii, M.; Nishimura, K.; Kamimura, K. Functions of chondroitin sulfate and heparan sulfate in the developing brain. Neurochem. Res. 2011, 36, 1228–1240, doi:10.1007/s11064-010-0324-y.
[3]
Ichijo, H. Proteoglycans as cues for axonal guidance in formation of retinotectal or retinocollicular projections. Mol. Neurobiol. 2004, 30, 23–33, doi:10.1385/MN:30:1:023.
[4]
Nishimura, K.; Ishii, M.; Kuraoka, M.; Kamimura, K.; Maeda, N. Opposing functions of chondroitin sulfate and heparan sulfate during early neuronal polarization. Neuroscience 2010, 169, 1535–1547, doi:10.1016/j.neuroscience.2010.06.027.
[5]
Kwok, J.C.; Warren, P.; Fawcett, J.W. Chondroitin sulfate: A key molecule in the brain matrix. Int. J. Biochem. Cell Biol. 2012, 44, 582–586.
Mikami, T.; Yasunaga, D.; Kitagawa, H. Contactin-1 is a functional receptor for neuroregulatory chondroitin sulfate-E. J. Biol. Chem. 2009, 284, 4494–4499, doi:10.1074/jbc.M809227200.
[8]
Shen, Y.; Tenney, A.P.; Busch, S.A.; Horn, K.P.; Cuascut, F.X.; Liu, K.; He, Z.; Silver, J.; Flanagan, J.G. PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 2009, 326, 592–596.
Snow, D.M.; Lemmon, V.; Carrino, D.A.; Caplan, A.I.; Silver, J. Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp. Neurol. 1990, 109, 111–130, doi:10.1016/S0014-4886(05)80013-5.
[12]
Snow, D.M.; Watanabe, M.; Letourneau, P.C.; Silver, J. A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth. Development 1991, 113, 1473–1485.
[13]
Brittis, P.A.; Canning, D.R.; Silver, J. Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science 1992, 255, 733–736.
[14]
Brittis, P.A.; Silver, J. Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. Proc. Natl. Acad. Sci. USA 1994, 91, 7539–7542.
[15]
Hoffman-Kim, D.; Lander, A.D.; Jhaveri, S. Patterns of chondroitin sulfate immunoreactivity in the developing tectum reflect regional differences in glycosaminoglycan biosynthesis. J. Neurosci. 1998, 18, 5881–5890.
[16]
Chung, K.Y.; Taylor, J.S.; Shum, D.K.; Chan, S.O. Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos. Development 2000, 127, 2673–2683.
[17]
Yick, L.W.; Wu, W.; So, K.F.; Yip, H.K.; Shum, D.K. Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons after spinal cord injury. Neuroreport 2000, 11, 1063–1067, doi:10.1097/00001756-200004070-00032.
[18]
Ichijo, H.; Kawabata, I. Roles of the telencephalic cells and their chondroitin sulfate proteoglycans in delimiting an anterior border of the retinal pathway. J. Neurosci. 2001, 21, 9304–9314.
[19]
Moon, L.D.; Asher, R.A.; Rhodes, K.E.; Fawcett, J.W. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat. Neurosci. 2001, 4, 465–466.
[20]
Becker, C.G.; Becker, T. Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. J. Neurosci. 2002, 22, 842–853.
[21]
Walz, A.; Anderson, R.B.; Irie, A.; Chien, C.B.; Holt, C.E. Chondroitin sulfate disrupts axon pathfinding in the optic tract and alters growth cone dynamics. J. Neurobiol. 2002, 53, 330–342, doi:10.1002/neu.10113.
Busch, S.A.; Silver, J. The role of extracellular matrix in CNS regeneration. Curr. Opin. Neurobiol. 2007, 17, 120–127, doi:10.1016/j.conb.2006.09.004.
[25]
Cafferty, W.B.; Bradbury, E.J.; Lidierth, M.; Jones, M.; Duffy, P.J.; Pezet, S.; McMahon, S.B. Chondroitinase ABC-mediated plasticity of spinal sensory function. J. Neurosci. 2008, 28, 11998–12009, doi:10.1523/JNEUROSCI.3877-08.2008.
[26]
Faissner, A.; Clement, A.; Lochter, A.; Streit, A.; Mandl, C.; Schachner, M. Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties. J. Cell Biol. 1994, 126, 783–799, doi:10.1083/jcb.126.3.783.
[27]
Fernaud-Espinosa, I.; Nieto-Sampedro, M.; Bovolenta, P. Differential effects of glycosaminoglycans on neurite outgrowth from hippocampal and thalamic neurones. J. Cell Sci. 1994, 107, 1437–1448.
[28]
Nadanaka, S.; Clement, A.; Masayama, K.; Faissner, A.; Sugahara, K. Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity. J. Biol. Chem. 1998, 273, 3296–3307.
[29]
Clement, A.M.; Sugahara, K.; Faissner, A. Chondroitin sulfate E promotes neurite outgrowth of rat embryonic day 18 hippocampal neurons. Neurosci. Lett. 1999, 269, 125–128, doi:10.1016/S0304-3940(99)00432-2.
[30]
Huxlin, K.R.; Sefton, A.J.; Schulz, M.; Bennett, M.R. Effect of proteoglycan purified from rat superior colliculus on the survival of murine retinal ganglion cells. Dev. Brain Res. 1993, 74, 207–217, doi:10.1016/0165-3806(93)90006-V.
[31]
Pizzorusso, T.; Medini, P.; Berardi, N.; Chierzi, S.; Fawcett, J.W.; Maffei, L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science 2002, 298, 1248–1251.
[32]
Pizzorusso, T.; Medini, P.; Landi, S.; Baldini, S.; Berardi, N.; Maffei, L. Structural and functional recovery from early monocular deprivation in adult rats. Proc. Natl. Acad. Sci. USA 2006, 103, 8517–8522.
[33]
Carulli, D.; Pizzorusso, T.; Kwok, J.C.; Putignano, E.; Poli, A.; Forostyak, S.; Andrews, M.R.; Deepa, S.S.; Glant, T.T.; Fawcett, J.W. Animals lacking link protein have attenuated perineuronal nets and persistent plasticity. Brain 2010, 133, 2331–2347, doi:10.1093/brain/awq145.
[34]
Miyata, S.; Komatsu, Y.; Yoshimura, Y.; Taya, C.; Kitagawa, H. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat. Neurosci. 2012, 15, 414–422, doi:10.1038/nn.3023.
[35]
Clement, A.M.; Nadanaka, S.; Masayama, K.; Mandl, C.; Sugahara, K.; Faissner, A. The DSD-1 carbohydrate epitope depends on sulfation, correlates with chondroitin sulfate D motifs, and is sufficient to promote neurite outgrowth. J. Biol. Chem. 1998, 273, 28444–28453.
[36]
Ueoka, C.; Kaneda, N.; Okazaki, I.; Nadanaka, S.; Muramatsu, T.; Sugahara, K. Neuronal cell adhesion, mediated by the heparin-binding neuroregulatory factor midkine, is specifically inhibited by chondroitin sulfate E. J. Biol. Chem. 2000, 275, 37407–37413.
[37]
Gilbert, R.J.; McKeon, R.J.; Darr, A.; Calabro, A.; Hascall, V.C.; Bellamkonda, R.V. CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension. Mol. Cell. Neurosci. 2005, 29, 545–558, doi:10.1016/j.mcn.2005.04.006.
[38]
Properzi, F.; Carulli, D.; Asher, R.A.; Muir, E.; Camargo, L.M.; van Kuppevelt, T.H.; ten Dam, G.B.; Furukawa, Y.; Mikami, T.; Sugahara, K.; Toida, T.; Geller, H.M.; Fawcett, J.W. Chondroitin 6-sulphate synthesis is up-regulated in injured CNS, induced by injury-related cytokines and enhanced in axon-growth inhibitory glia. Eur. J. Neurosci. 2005, 21, 378–390, doi:10.1111/j.1460-9568.2005.03876.x.
[39]
Ishii, M.; Maeda, N. Oversulfated chondroitin sulfate plays critical roles in the neuronal migration in the cerebral cortex. J. Biol. Chem. 2008, 283, 32610–32620, doi:10.1074/jbc.M806331200.
Shinohara, Y.; Sota, H.; Kim, F.; Shimizu, M.; Gotoh, M.; Tosu, M.; Hasegawa, Y. Use of a biosensor based on surface plasmon resonance and biotinyl glycans for analysis of sugar binding specificities of lectins. J. Biochem. 1995, 117, 1076–1082.
[45]
Sugiura, N.; Sakurai, K.; Hori, Y.; Karasawa, K.; Suzuki, S.; Kimata, K. Preparation of lipid-derivatized glycosaminoglycans to probe a regulatory function of the carbohydrate moieties of proteoglycans in cell-matrix interaction. J. Biol. Chem. 1993, 268, 15779–15787.
[46]
Ando, S.; Sugiura, N.; Kimata, K.; Ichijo, H. Influences of retinal axons on the cultural substrate containing biotin-conjugated chondroitin sulfate in vitro. Anat. Sci. Int. 2010, 85, 189–193, doi:10.1007/s12565-010-0076-4.
[47]
Hendrickson, W.A.; P？hler, A.; Smith, J.L.; Satow, Y.; Merritt, E.A.; Phizackerley, R.P. Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. Proc. Natl. Acad. Sci. USA 1989, 86, 2190–2194.
[48]
Ichijo, H. Restricted distribution of D-unit–rich chondroitin sulfate carbohydrate chains in the neuropil encircling the optic tract and on a subset of retinal axons in chick embryos. J. Comp. Neurol. 2006, 495, 470–479, doi:10.1002/cne.20892.
[49]
Simbo, M.; Ando, S.; Sugiura, N.; Kimata, K.; Ichijo, H. Moderate repulsive effects of E-unit–containing chondroitin sulfate (CSE) on behavior of retinal growth cones. Brain Res. 2013, 1491, 34–43, doi:10.1016/j.brainres.2012.11.011.
[50]
Fournier, A.E.; Nakamura, F.; Kawamoto, S.; Goshima, Y.; Kalb, R.G.; Strittmatter, S.M. Semaphorin3A enhances endocytosis at sites of receptor-F-actin colocalization during growth cone collapse. J. Cell Biol. 2000, 149, 411–422, doi:10.1083/jcb.149.2.411.
[51]
Weinl, C.; Drescher, U.; Lang, S.; Bonhoeffer, F.; Loschinger, J. On the turning of Xenopus retinal axons induced by ephrin-A5. Development 2003, 130, 1635–1643, doi:10.1242/dev.00386.
[52]
Sugiura, N.; Shioiri, T.; Chiba, M.; Sato, T.; Narimatsu, H.; Kimata, K.; Watanabe, H. Construction of a chondroitin sulfate library with defined structures and analysis of molecular interactions. J. Biol. Chem. 2012, 287, 43390–43400.
[53]
Arnosti, C. Fluorescent derivatization of polysaccharides and carbohydrate-containing biopolymers for measurement of enzyme activities in complex media. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 2003, 793, 181–191, doi:10.1016/S1570-0232(03)00375-1.
