We have conducted studies showing that the the LAR family of receptor protein tyrosine phosphatases are are binding partners for proteoglycan 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. We have identified a novel binding site in Receptor Protein Tyrosine Phosphatase Sigma that binds Heparin Sulfate. In addition our data point to an additional receptor that binds bioactive CSPGs. A publication describing these results is in preparation. We demonstrated the the Lipid Phosphate Phosphatase-Related Proteins (LPPRs) act in concert to modulate cellular physiology. We find that they associate with each other in cells, and that this association increases the bioactivity of these proteins. A paper describing these results was published. We have created knockout mice for the LPPR-1 and LPPR-3 and are now characterizing these mice. We have found that xylosides, compounds that are used to alter proteoglycan GAG chain composition, have significant actions at concentrations lower than those previously reported to reduce GAG chains can alter growth cone morphology. Evidence points to a novel signaling mechanism triggered by xylsides only at low concentrations. In collaboration with Dr. Jeffrey Urbach of Georgetown University, we are investigating the role of stiffness in controlling axonal growth. We have shown than neurons grow differently on substrates of different stiffness, and are now investigating the role of stiffness in neuronal guidance.
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