Publication Date:
2009-10-17
Description:
Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTPsigma, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPsigma. In culture, PTPsigma(-/-) neurons show reduced inhibition by CSPG. A PTPsigma fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPsigma gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPsigma can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811318/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2811318/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shen, Yingjie -- Tenney, Alan P -- Busch, Sarah A -- Horn, Kevin P -- Cuascut, Fernando X -- Liu, Kai -- He, Zhigang -- Silver, Jerry -- Flanagan, John G -- R01 EY011559/EY/NEI NIH HHS/ -- R01 NS025713/NS/NINDS NIH HHS/ -- R37 HD029417/HD/NICHD NIH HHS/ -- R37 NS025713/NS/NINDS NIH HHS/ -- R37 NS025713-22/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 23;326(5952):592-6. doi: 10.1126/science.1178310. Epub 2009 Oct 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19833921" target="_blank"〉PubMed〈/a〉
Keywords:
Aggrecans/metabolism
;
Animals
;
Astrocytes/metabolism
;
Axons/physiology
;
Binding Sites
;
Cells, Cultured
;
Chondroitin Sulfate Proteoglycans/chemistry/*metabolism
;
Chondroitin Sulfates/metabolism
;
Female
;
Ganglia, Spinal/cytology/metabolism
;
Ligands
;
Mice
;
*Nerve Regeneration
;
Nerve Tissue Proteins/chemistry/*metabolism
;
Neurites/physiology
;
Neurons/*physiology
;
Protein Binding
;
Protein Interaction Domains and Motifs
;
Proteoglycans/chemistry/*metabolism
;
Receptor-Like Protein Tyrosine Phosphatases, Class
;
2/chemistry/genetics/*metabolism
;
Recombinant Fusion Proteins/chemistry/metabolism
;
Spinal Cord/metabolism/pathology
;
Spinal Cord Injuries/*metabolism/pathology/physiopathology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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