Chondroitin Sulfate Glycosaminoglycans Regulate Distinct Cell Surface Receptor-Mediated Neuronal Functions

Abstract

Chondroitin sulfate (CS) chains, a class of sulfated glycosaminoglycan (GAG) polysaccharides, are major extra/pericellular components that function as microenvironmental cues during neuronal development and the regeneration of injured neurons. Interestingly, CS chains exert both facilitatory and inhibitory effects on neurite outgrowth. Such bidirectional CS chain effects are ascribable to their own structural divergence that could be generated via distinct enzymatic modifications. CS chains have long been considered as passive structural scaffolds that often behave as co-receptors and/or reservoirs for various humoral factors. However, the recent identification of cell surface receptor molecules with binding preferences to distinct CS structures has provided new insight into a novel CS chain effector mechanism functioning as dynamic extra/pericellular signaling ligands that could directly control the corresponding receptor-mediated signaling pathways. This new concept might also support the functional complexity of CS chains in neurobiological events.