Protein Tyrosine Phosphatase sigma in Proteoglycan-Mediated Neural Regeneration Regulation

Abstract

The receptor-type protein tyrosine phosphatase PTP sigma mediates neural development and regeneration. Early studies on the ligands of PTPs identified heparan sulfate proteolycan (HSPG) as a ligand. Binding of HSPG to PTPs plays a critical role in axon guidance and synapse formation. PTPs is also a receptor for chondroitin sulfate proteoglycan (CSPG). CSPG is deposited in high concentration at sites of neural injury. The deposited CSPG inhibits neural regeneration and axonal growth via PTPs. The crystal structure of N-terminal immunoglobulin-like domains of PTPs shows that the glycan binding site forms an elliptical surface patch of similar to 35 by 24 angstrom, which interacts with sulfate groups of HSPG and CSPG. In this review, we focus on the structural and functional mechanisms for the neural regeneration regulation by different types of proteoglycans. We also discuss recent results on induction of neural regeneration in the stroke model and neural transplantation. The mechanistic understanding of relationships between proteoglycans and PTPs provides new therapeutic opportunities against diseases with impaired neural regeneration.