Figure 4.

Mechanisms for CSPG inhibition. Proteoglycans are a heterogenous class of extracellular proteins with distinct protein core structures bearing covalently attached sulfated glycosaminoglycan (GAG) side chains. Prominent members of neural proteoglycans bearing heparan sulfate GAG chains (HSPGs) include the syndecans, glycpicans and agrin. Chondroitin sulfate GAG bearing proteoglycans (CSPGs) include members of the lectican family (neurocan, aggrecan, versican, and brevican). The leukocyte antigen-related (LAR) subfamily of receptor protein tyrosine phosphatases (RPTPs) includes the mammalian members LAR, RPTPσ and RPTPδ. LAR type RPTPs are transmembrane proteins with cell adhesion molecule-like ectodomains and a large cytoplasmic region with two conserved phosphatase domains. The Drosophila homolog of LAR-RPTPσ-RPTPδ is called DLAR and is a functional receptor for the fly HSPGs syndecan and glypican (dally-like). Avian RPTPσ binds directly to the HSPGs agrin and collagen XVIII. In addition, CSPGs belonging to the lectican family (including neurocan and aggrecan) bind to the first Ig-like domain of mouse RPTPσ to signal neuronal growth inhibition. The interaction between lecticans and RPTPσ is direct, depends on the presence of CS-GAG chains, and is sensitive to chondroitinase ABC treatment.