A Novel Cytoskeletal Action of Xylosides

Abstract Proteoglycan glycosaminoglycan (GAG) chains are attached to a serine residue in the protein through a linkage series of sugars, the first of which is xylose. Xylosides are chemicals which compete with the xylose at the enzyme xylosyl transferase to prevent the attachment of GAG chains to proteins. These compounds have been employed at concentrations in the millimolar range as tools to study the role of GAG chains in proteoglycan function. In the course of our studies with xylosides, we conducted a dose-response curve for xyloside actions on neural cells. To our surprise, we found that concentrations of xylosides in the nanomolar to micromolar range had major effects on cell morphology. These effects are due to changes in cytoskeletal dynamics. Concentrations of xylosides which were effective in altering morphology did not alter GAG chain synthesis rates, nor did they produce any changes in gene expression as determined by RNAseq of treated cells. These observations support a novel action of xylosides on neuronal cells.