We are expanding the range of assay techniques that will allow us to understand the sulfation code in chondroitin sulfate glycosaminoglycan (CS-GAG) chains. These assay techniques take advantage of specific chromatography techniques (ion exchange, hydrophilicity) to separate the different disaccharides and monosaccharides that comprise the GAG chains. This is the only technique capable of doing this. We have also initiated mass spectrometric analysis of these separated GAG chains to begin to determine the sequence of sulfations on the different parts of the GAG chain. Our results indicate that the sulfation pattern of the non-reducing end of the GAG chain is a major determinant of CS signaling. A publication describing these results is in preparation. We published a systems biology study to understand CSPG signaling in cells. We identified a number of proteins whose phosphorylation is changed rapidly as neurons are exposed to CSPGs. Our results indicate that there are a number of different signaling pathways inovlved in response to CSPGs in cells, but that the changes in phosphorylations are modest. These results suggest that CSPG may modulate many difference cellular functions. We are conducting studies showing that the the LAR family of receptor protein tyrosine phosphatases are are binding partners for CS GAG chains. The binding of the different family members are not all the same. We have identified different regions in the extracellular domains of these molecules that bind GAG chains with different sulfation patterns. In addition our data point to an additional receptor that binds bioactive CSPGs. A publication describing these results is in preparation.

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National Heart, Lung, and Blood Institute
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