Abstract
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.
MeSH terms
-
Aggrecans / metabolism
-
Animals
-
Astrocytes / metabolism
-
Axons / physiology
-
Binding Sites
-
Cells, Cultured
-
Chondroitin Sulfate Proteoglycans / chemistry
-
Chondroitin Sulfate Proteoglycans / metabolism*
-
Chondroitin Sulfates / metabolism
-
Female
-
Ganglia, Spinal / cytology
-
Ganglia, Spinal / metabolism
-
Ligands
-
Mice
-
Nerve Regeneration*
-
Nerve Tissue Proteins / chemistry
-
Nerve Tissue Proteins / metabolism*
-
Neurites / physiology
-
Neurocan
-
Neurons / physiology*
-
Protein Binding
-
Protein Interaction Domains and Motifs
-
Proteoglycans / chemistry
-
Proteoglycans / metabolism*
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / chemistry
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
-
Recombinant Fusion Proteins / chemistry
-
Recombinant Fusion Proteins / metabolism
-
Spinal Cord / metabolism
-
Spinal Cord / pathology
-
Spinal Cord Injuries / metabolism*
-
Spinal Cord Injuries / pathology
-
Spinal Cord Injuries / physiopathology
Substances
-
Aggrecans
-
Chondroitin Sulfate Proteoglycans
-
Ligands
-
Ncan protein, mouse
-
Nerve Tissue Proteins
-
Neurocan
-
Proteoglycans
-
Recombinant Fusion Proteins
-
Chondroitin Sulfates
-
Ptprs protein, mouse
-
Receptor-Like Protein Tyrosine Phosphatases, Class 2