The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
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
In the citing paper
“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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Citations
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
Cited by
Sorted by citations
The Biology of Regeneration Failure and Success After Spinal Cord Injury
Tran, A. P., Warren, P. M., & Silver, J. (2018) · Physiological Reviews · doi:10.1152/physrev.00017.2017 · Cited by 903
Moving beyond the glial scar for spinal cord repair
Bradbury, E. J., & Burnside, E. R. (2019) · Nature Communications · doi:10.1038/s41467-019-11707-7 · Cited by 774
The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function
Fawcett, J. W., Oohashi, T., & Pizzorusso, T. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0196-3 · Cited by 589
Self-citationPathophysiology of the brain extracellular matrix: a new target for remyelination
Lau, L. W., Cua, R., Keough, M. B., Haylock-Jacobs, S., & Yong, V. W. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3550 · Cited by 549
Extracellular matrix and perineuronal nets in CNS repair
Kwok, J. C. F., Dick, G., Wang, D., & Fawcett, J. W. (2011) · Developmental Neurobiology · doi:10.1002/dneu.20974 · Cited by 395
Self-citation
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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