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Integrin Activation Promotes Axon Growth on Inhibitory Chondroitin Sulfate Proteoglycans by Enhancing Integrin Signaling
Open accessAbstract
Chondroitin sulfate proteoglycans (CSPGs) are upregulated after CNS lesions, where they inhibit axon regeneration. In order for axon growth and regeneration to occur, surface integrin receptors must interact with surrounding extracellular matrix molecules. We have explored the hypothesis that CSPGs inhibit regeneration by inactivating integrins and that forcing integrins into an active state might overcome this inhibition. Using cultured rat sensory neurons, we show that the CSPG aggrecan inhibits laminin-mediated axon growth by impairing integrin signaling via decreasing phosphorylated FAK (pFAK) and pSrc levels, without affecting surface integrin levels. Forcing integrin activation and signaling by manganese or an activating antibody TS2/16 reversed the inhibitory effect of aggrecan on mixed aggrecan/laminin surfaces, and enhanced axon growth from cultured rat sensory neurons (manganese) and human embryonic stem cell-derived motoneurons (TS2/16). The inhibitory effect of Nogo-A can also be reversed by integrin activation. These results suggest that inhibition by CSPGs can act via inactivation of integrins, and that activation of integrins is a potential method for improving axon regeneration after injury.
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“Previous studies revealed an interaction between β1-integrins and CSPGs (Tan et al., 2011;Wu et al., 2002).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Tan et al., 2011
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“A potential mechanism of CSPG-mediated repulsion may be through control of integrins.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Tan et al., 2011
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“Specifically, CSPGs, and particularly their GAG moieties, may act by i) binding to a specific receptor; ii) blocking the growth-promoting activity of integrins; iii) presenting growth-inhibitory proteins.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Tan et al., 2011
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Cites
Hynes (2002) · doi:10.1016/s0092-8674(02)00971-6 · Cited by 8,606
Regeneration beyond the glial scar
Silver, J., & Miller, J. H. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1326 · Cited by 3,151
Integrin-regulated FAK–Src signaling in normal and cancer cells
Mitra, S. K., & Schlaepfer, D. D. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.08.011 · Cited by 1,641
Focal adhesion kinase: the first ten years
Parsons, J. T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00373 · Cited by 1,389
Kindlin-3 is essential for integrin activation and platelet aggregation
Moser, M., Nieswandt, B., Ussar, S., Požgajová, M., & Fässler, R. (2008) · Nature Medicine · doi:10.1038/nm1722 · Cited by 700
PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration
Shen, Y., Tenney, A. P., Busch, S. A., Horn, K. P., Cuascut, F. X., Liu, K., He, Z., Silver, J., & Flanagan, J. G. (2009) · Science · doi:10.1126/science.1178310 · Cited by 682
Kindlin-2 controls bidirectional signaling of integrinsPreprint
Montañez, E., Ussar, S., Schifferer, M., Bösl, M. R., Zent, R., Moser, M., & Fässler, R. (2008) · Genes & Development · doi:10.1101/gad.469408 · Cited by 452
Monnier, P. P., Sierra, A., Schwab, J. M., Henke‐Fahle, S., & Mueller, B. K. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(02)00035-0 · Cited by 407
Tang, X., Davies, J. E., & Davies, S. J. A. (2002) · Journal of Neuroscience Research · doi:10.1002/jnr.10523 · Cited by 391
The cell biology of neuronal navigation
Song, H., & Poo, M. (2001) · Nature Cell Biology · doi:10.1038/35060164 · Cited by 379
Koprivica, V., Cho, K., Park, J. B., Yiu, G. C., Atwal, J. K., Gore, B. B., Kim, J. A., Lin, E., Tessier‐Lavigne, M., Chen, D. F., et al. (2005) · Science · doi:10.1126/science.1115462 · Cited by 363
Regulation of Integrin α5β1-Fibronectin Interactions by Divalent Cations
Mould, A. P., Akiyama, S. K., & Humphries, M. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.44.26270 · Cited by 328
Sivasankaran, R., Pei, J., Wang, K., Zhang, Y. P., Shields, C. B., Xu, X., & He, Z. (2004) · Nature Neuroscience · doi:10.1038/nn1193 · Cited by 314
Bazzoni, G., Shih, D.-T., Buck, C. A., & Hemler, M. E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25570 · Cited by 276
Nieswandt, B., Moser, M., Pleines, I., Varga-Szabó, D., Monkley, S., Critchley, D. R., & Fässler, R. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20071827 · Cited by 273
Semaphorin function in neural plasticity and disease
Pasterkamp, R. J., & Giger, R. J. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.06.001 · Cited by 237
Suppression of Rho-kinase activity promotes axonal growth on inhibitory CNS substrates
Borisoff, J., Chan, C. C. M., Hiebert, G. W., Oschipok, L. W., Robertson, G. S., Zamboni, R. J., Steeves, J. D., & Tetzlaff, W. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(02)00032-5 · Cited by 211
Regulating actin dynamics in neuronal growth cones by ADF/cofilin and Rho family GTPases
Kuhn, T. B., Meberg, P. J., Brown, M. D., Bernstein, B. W., Minamide, L. S., Jensen, J. R., Okada, K., Soda, E. A., & Bamburg, J. R. (2000) · Journal of Neurobiology · doi:10.1002/1097-4695(200008)44:2 · Cited by 189
Structural basis for the inhibition of activin signalling by follistatin
Harrington, A. E., Morris-Triggs, S. A., Ruotolo, B. T., Robinson, C. V., Ohnuma, S., & Hyvönen, M. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601000 · Cited by 166
α9 Integrin Promotes Neurite Outgrowth on Tenascin-C and Enhances Sensory Axon Regeneration
Andrews, M. R., Czvitkovich, S., Dassie, E., Vogelaar, C. F., Faissner, A., Blits, B., Gage, F. H., ffrench‐Constant, C., & Fawcett, J. W. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0759-09.2009 · Cited by 161
Self-citationMould, A. P., Askari, J. A., Aota, S., Yamada, K. M., Irie, A., Takada, Y., Mardon, H. J., & Humphries, M. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.28.17283 · Cited by 157
Regulation of Neurite Outgrowth by Integrin Activation
Ivins, J. K., Yurchenco, P. D., & Lander, A. D. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-17-06551.2000 · Cited by 152
Hu, F., & Strittmatter, S. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1068-07.2008 · Cited by 137
Role of integrins in the peripheral nervous system
Previtali, S. C., Feltri, M. L., Archelos, J. J., Quattrini, A., Wrabetz, L., & Hartung, H.-P. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00045-9 · Cited by 122
White matter inhibitors in CNS axon regeneration failure
Xie, F., & Zheng, B. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.07.005 · Cited by 104
Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan
Afshari, F. T., Kwok, J. C., White, L., & Fawcett, J. W. (2010) · Glia · doi:10.1002/glia.20970 · Cited by 103
Self-citationOn the existence of a cartilage‐like proteoglycan and link proteins in the central nervous system
Asher, R. A., Scheibe, R. J., Keiser, H. D., & Bignami, A. (1995) · Glia · doi:10.1002/glia.440130406 · Cited by 100
Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism
Zhou, F., Walzer, M., Wu, Y.-H., Zhou, J., Dedhar, S., & Snider, W. D. (2006) · Journal of Cell Science · doi:10.1242/jcs.03016 · Cited by 98
Bazzoni, G., Ma, L., Blue, M., & Hemler, M. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.12.6670 · Cited by 92
Patani, R., Compston, A., Puddifoot, C. A., Wyllie, D. J. A., Hardingham, G. E., Allen, N. D., & Chandran, S. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007327 · Cited by 88
Self-citationReichardt, L. F., Bixby, J. L., Hall, D. E., Ignatius, M. J., Neugebauer, K. M., & Tomaselli, K. J. (1989) · Developmental Neuroscience · doi:10.1159/000111910 · Cited by 71
Integrin signaling is integral to regeneration
Lemons, M. L., & Condic, M. L. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.05.027 · Cited by 65
Lemons, M. L., & CONDIC, M. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.06.008 · Cited by 47
Manganese induces neurite outgrowth in PC12 cells via upregulation of αv integrins
Lein, P. J., Gallagher, P. J., Amodeo, J., Howie, H. L., & Roth, J. A. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02943-7 · Cited by 46
ADP-ribosylation of integrin α7 modulates the binding of integrin α7β1 to laminin
Zhao, Z., Gruszczynska‐Biegala, J., & Żółkiewska, A. (2004) · Biochemical Journal · doi:10.1042/bj20040590 · Cited by 41
Classification of ‘activation’ antibodies against integrin β1 chain
Tsuchida, J., Ueki, S., Saito, Y., & Takagi, J. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01206-4 · Cited by 37
Chan, C. C. M., Roberts, C. R., Steeves, J. D., & Tetzlaff, W. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21522 · Cited by 37
Li, H., Domowicz, M. S., Hennig, A. K., & Schwartz, N. B. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00269-x · Cited by 32
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Metadata
- Authors
- Tan, C. L., Kwok, J. C. F., Patani, R., ffrench-Constant, C., Chandran, S., & Fawcett, J. W.
- Affiliations
- University of Cambridge (GB)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-04-27
- Volume
- 31
- Issue
- 17
- Pages
- 6289-6295
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3116378
- OpenAlex
- W2068815747
- Cited by
- 160
- References
- 38
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 1 · 2023: 5 · 2022: 7 · 2021: 12 · 2020: 10 · 2019: 10 · 2018: 16 · 2017: 7 · 2016: 8 · 2015: 13 · 2014: 19 · 2013: 12 · 2012: 19
- FWCI
- 7.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation (SP/10/003/28287)
- Motor Neurone Disease Association
- European Commission
- Henry Smith Charity
- John and Lucille Van Geest Foundation
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- integrin activation, chondroitin sulfate proteoglycans, axon regeneration, aggrecan, laminin, focal adhesion kinase, Src kinase, Nogo-A, sensory neurons, motor neurons, extracellular matrix, central nervous system injury, integrin signaling
- MeSH terms
- Animals, Antibodies, Axons, Cells, Cultured, Dose-Response Relationship, Drug, Drug Interactions, Ganglia, Spinal, Gene Expression Regulation, Humans, Male, Manganese, Neural Inhibition, Neurons, Chondroitin Sulfate Proteoglycans, Time Factors, Signal Transduction, Integrins, Rats, Sprague-Dawley, Chondroitin ABC Lyase, Lamins, Rats, Aggrecans
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