The role of keratan sulfate regulating neural network rearrangement

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We have revealed that keratan sulfate (KS), which is a kind ofglycosaminoglycan, strongly inhibits the neurite outgrowth as well as chondroitin sulfate (CS). In this study, I aimed the identification of KS/CSPG and the evaluation of the mechanism recognizing KS/CSPG by neurons. KS/CSPGs were isolated from the injured spinal cords and reactive-astrocytes stimulated by the growth factors using column chromatography, and were identified by the shot-gun proteomics method. Phosphacan was mainly identified as the inhibitory KS/CSPG. Interestingly, the inhibitory KS/CSPG isolated from postnatal 1 day rat brain was also identified as phosphacan. Therefore, I suggest that the injured neurons and developing neurons recognize KS/CSPG in the common manner. In addition, the recombinant KS-bearing phaophacan strongly inhibited the neurite outgrowth, and the deletion of KS binding domain of phosphacan ameliorated the neurite outgrowth. From these result, I suggest that neurons strongly recognize keratan sulfate on phosphacan and inhibit neurite outgrowth.