MODULATION OF NEURITE-PROMOTING PROTEOGLYCANS BY NEURONAL DIFFERENTIATION

A human cell line committed to neuronal lineage was used to examine th e influence of differentiation on proteoglycan synthesis and function. Where the LA-N-2 cells were stimulated to differentiate towards a phe notype of cholinergic neurons, proteoglycans of the heparan sulphate c lass increased relative to chondroitin sulphate proteoglycans and disp layed more homogenously shorter glycosaminoglycan chains with increasi ng degrees of sulphation. The changes were accompanied by increasing p otency of the heparan sulphate proteoglycans in neurite growth-promoti ng activity when immobilized on a laminin substrate. These studies beg in to address the role of activity-independent growth and differentiat ion on the synthesis and release by neurons of neurite growth-promotin g proteoglycans. The observations have implications for understanding the role of proteoglycan overexpression and the production of dystroph ic neurites in Alzheimer disease.