PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

• Published in: Science (American Association for the Advancement of Science) Vol. 326; no. 5952; pp. 592 - 596
• Main Authors: Shen, Yingjie, Tenney, Alan P., Busch, Sarah A., Horn, Kevin P., Cuascut, Fernando X., Liu, Kai, He, Zhigang, Silver, Jerry, Flanagan, John G.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 23.10.2009
• Subjects: Astrocytes; Axons; Biological and medical sciences; Central nervous system; Fundamental and applied biological sciences. Psychology; Lesions; Ligands; Neurons; Proteoglycans; Receptors; Spinal cord; Sulfates; Vertebrates: nervous system and sense organs; Transmembrane protein; Proteoglycan; Immunoglobulins; Spinal cord; Enzyme; Central nervous system; Phosphoric monoester hydrolases; Axon; Esterases; In vitro; Regeneration; Hydrolases; Chondroitin sulfate; Inhibition; Lesion; Protein-tyrosine-phosphatase; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1178310

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, PTPa, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPσ. In culture,$PTP\sigma ^{ - / - } $neurons show reduced inhibition by CSPG. A PTPa fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPa gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPa can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.