During development, guidance cues mediate axon guidance such that synaptic connections made give rise to a properly functioning central nervous system. Chondroitin sulfate proteoglycans (CSPGs) inhibit axon outgrowth by interacting with their transmembrane receptor protein tyrosine phosphatase sigma (RPTPσ). Glypicans (GPCs) also interact with RPTPσ via their heparin sulfate glycosaminoglycans. Due to their GPI-anchor, GPCs are present in the lipid raft region of the membrane. Here it is shown that in retinal explants cultured on CSPGs treated with methyl beta cyclodextrin (MβCD), axon outgrowth is promoted, implying that RPTPσ may be associated with the lipid raft region to mediate the effect of CSPGs. When either exogenous GPCs are added or endogenous GPCs are silenced, there is a significant rescue in axon outgrowth on CSPGs. This suggests that GPCs may play a role in recruiting RPTPσ into the lipid raft region of the membrane to mediate the inhibitory effect of CSPGs.M.Sc
