Differentiation/regeneration of oligodendrocytes entails the assembly of a cell-associated matrix

Abstract

Oligodendrocytes assemble and maintain CNS myelin. We have shown that adhesion of ovine oligodendrocytes to the substratum, GRASP — a novel, horse serum heparin-binding glycoprotein — initiates their myelinogenic phenotype. Synthesis and vectorial transport to the plasma membrane of heparan sulfate proteoglycans is one of the many events that ensue upon adhesion. Proteoglycans play key roles in defining the line of communication between cells and their microenvironment. The nature of their association with cells varies. Often, proteoglycans are part of a complex extracellular network that either surrounds cells or is restricted to smaller areas of their surface. Such extracellular matrices form an integral part of the machinery that regulates cell function. As part of an effort to delineate the events and identify the molecules involved in the adhesion-induced-regeneration and possibly in differentiation of OLGs, we have undertaken to define the full repertoire of OLG proteoglycans. Oligodendrocytes express surface-associated proteoglycans and also secrete them to the medium. However, we observed a clear distinction between secreted and surface-associated proteoglycans in terms of types, temporal regulation and spacial distribution. Oligodendrocytes secrete chondroitin sulfate proteoglycans and keratan sulfate proteoglycans but have only heparan sulfate proteoglycans associated with their surface. Secreted proteoglycans are temporally modulated but adhesion-independent, whereas surface-associated proteoglycans are adhesion-induced. Herein, we present the biochemical characterization of oligodendrocyte proteoglycans. We report that a significant fraction of the surface-associated heparan sulfate proteoglycans are assembled into a cell-associated matrix. This finding is important. First, it reveals a closer parallel than hitherto documented with events that signal Schwann cell myelination. Second, it implicates HSPGs in the establishment of OLG differentiated phenotype. Third, it brings OLGs in tune with other cell types where the ECM (broadly defined) is critical for the orchestration of cues that generate tissue-specific gene expression and phenotypes.