Chondroitin sulfate proteoglycans in neural development and plasticity.

Abstract

PTPzeta and lectican family members are major chondroitin sulfate proteoglycans (CS-PGs) in the brain, which bind with many proteins via core protein and CS portions. Recent studies revealed that the oversulfated structures in CS constitute high affinity binding sites for various growth factors and axon guidance molecules, and play important roles in the proliferation of neural progenitor cells, neurite extension and neuronal migration. PTPzeta uses pleiotrophin as a ligand. The CS portion of PTPzeta constitutes a part of the pleiotrophin-binding site, and oversulfated D unit increases the binding affinity. Pleiotrophin-PTPzeta signaling regulates the morphogenesis of Purkinje cell by controlling the tyrosine phosphorylation of a Notch-related transmembrane protein, DNER. In the brain of adult animals, a subset of neurons are surrounded by CS-PG-rich extracellular matrix called perineuronal net, in which lecticans form complexes with hyaluronic acid and tenascin-R. CS-PGs in the perineuronal net regulate ocular dominance plasticity in the visual cortex by enhancing the uptake of Otx2 homeoprotein by parvalbumin-positive interneurons in a CS-dependent manner. These studies revealed unexpectedly complex mechanisms of CS-PG functions.