As axons extend outward, whether in the course of normal development or in regenerating after damage, they encounter an environment that includes proteoglycans. The chondroitin sulfate proteoglycans tend to inhibit axon growth, and the heparan sulfate proteoglycans tend to have the opposite effect. Both proteoglycans can signal through the same receptor, RPTPσ. Studying neurons from the mouse dorsal root ganglion, Coles et al. found that both types of proteoglycan used the same binding site on the receptor. However, heparan sulfate binding leads to receptor oligomerization, unlike chondroitin sulfate. Clustering of the receptors thus appears to generate an environment that encourages axonal growth.
C. H. Coles, Y. Shen, A. P. Tenney, C. Siebold, G. C. Sutton, W. Lu, J. T. Gallagher, E. Y. Jones, J. G. Flanagan, A. R. Aricescu, Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. Science 332, 484–488 (2011). [Abstract] [Full Text]