dc.contributor.author | Sheng, Morgan Hwa-Tze | |
dc.contributor.author | Fisher, Daniel | |
dc.contributor.author | Xing, Bin | |
dc.contributor.author | Dill, John | |
dc.contributor.author | Li, Hui | |
dc.contributor.author | Hoang, Hai Hiep | |
dc.contributor.author | Zhao, Zhenze | |
dc.contributor.author | Yang, Xiao-Li | |
dc.contributor.author | Bachoo, Robert | |
dc.contributor.author | Cannon, Stephen | |
dc.contributor.author | Longo, Frank M. | |
dc.contributor.author | Silver, Jerry | |
dc.contributor.author | Li, Shuxin | |
dc.date.accessioned | 2012-09-20T16:46:39Z | |
dc.date.available | 2012-09-20T16:46:39Z | |
dc.date.issued | 2011-10 | |
dc.date.submitted | 2011-08 | |
dc.identifier.issn | 0270-6474 | |
dc.identifier.issn | 1529-2401 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/73069 | |
dc.description.abstract | Chondroitin sulfate proteoglycans (CSPGs) are a family of extracellular matrix molecules with various functions in regulating tissue morphogenesis, cell division, and axon guidance. A number of CSPGs are highly upregulated by reactive glial scar tissues after injuries and form a strong barrier for axonal regeneration in the adult vertebrate CNS. Although CSPGs may negatively regulate axonal growth via binding and altering activity of other growth-regulating factors, the molecular mechanisms by which CSPGs restrict axonal elongation are not well understood. Here, we identified a novel receptor mechanism whereby CSPGs inhibit axonal growth via interactions with neuronal transmembrane leukocyte common antigen-related phosphatase (LAR). CSPGs bind LAR with high affinity in transfected COS-7 cells and coimmunoprecipitate with LAR expressed in various tissues including the brain and spinal cord. CSPG stimulation enhances activity of LAR phosphatase in vitro. Deletion of LAR in knock-out mice or blockade of LAR with sequence-selective peptides significantly overcomes neurite growth restrictions of CSPGs in neuronal cultures. Intracellularly, CSPG–LAR interaction mediates axonal growth inhibition of neurons partially via inactivating Akt and activating RhoA signals. Systemic treatments with LAR-targeting peptides in mice with thoracic spinal cord transection injuries induce significant axon growth of descending serotonergic fibers in the vicinity of the lesion and beyond in the caudal spinal cord and promote locomotor functional recovery. Identification of LAR as a novel CSPG functional receptor provides a therapeutic basis for enhancing axonal regeneration and functional recovery after CNS injuries in adult mammals. | en_US |
dc.description.sponsorship | Paralyzed Veterans of America (Grant 2584) | en_US |
dc.description.sponsorship | Paralyzed Veterans of America (Grant 2516) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (Grant 1R21 NS066114-01A1) | en_US |
dc.language.iso | en_US | |
dc.publisher | Society for Neuroscience | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1523/jneurosci.1737-11.2011 | en_US |
dc.rights | Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. | en_US |
dc.source | SFN | en_US |
dc.title | Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Fisher, D. et al. “Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors.” Journal of Neuroscience 31.40 (2011): 14051–14066. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences | en_US |
dc.contributor.department | Picower Institute for Learning and Memory | en_US |
dc.contributor.department | RIKEN-MIT Center for Neural Circuit Genetics | en_US |
dc.contributor.mitauthor | Sheng, Morgan Hwa-Tze | |
dc.relation.journal | Journal of Neuroscience | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Fisher, D.; Xing, B.; Dill, J.; Li, H.; Hoang, H. H.; Zhao, Z.; Yang, X.-L.; Bachoo, R.; Cannon, S.; Longo, F. M.; Sheng, M.; Silver, J.; Li, S. | en |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |