EXPRESSION OF A BETA(1)-RELATED INTEGRIN BY OLIGODENDROGLIA IN PRIMARY CULTURE - EVIDENCE FOR A FUNCTIONAL-ROLE IN MYELINATION

We have investigated the expression of integrins by rat oligodendrogli a grown in primary culture and the functional role of these proteins i n myelinogenesis. Immunochemical analysis, using antibodies to a numbe r of alpha and beta integrin subunits, revealed that oligodendrocytes express only one detectable integrin receptor complex (alpha(OL)beta(O L)). This complex is immunoprecipitated by a polyclonal anti-human bet a(1) integrin subunit antibody. In contrast, astrocytes, the other maj or glial cell type in brain, express multiple integrins including alph a(1) beta(1), alpha(3) beta(1), and alpha(5) beta(1) complexes that ar e immunologically and electrophoretically indistinguishable from integ rins expressed by rat fibroblasts. The beta subunit of the oligodendro cyte integrin (beta(OL)) and rat fibroblast beta(1) have different ele ctrophoretic mobilities in SDS-PAGE. However, the two beta subunits ap pear to be highly related based on immunological cross-reactivity and one-dimensional peptide mapping. After removal of N-linked carbohydrat e chains, beta(OL) and beta(1) comigrated in SDS-PAGE and peptide maps of the two deglycosylated subunits were identical, suggesting differe ntial glycosylation of beta(1) and beta(OL) accounts entirely for thei r size differences. The oligodendrocyte alpha subunit, alpha(OL), was not immunoprecipitated by antibodies against well. characterized alpha chains which are known to associate with beta(1) (alpha(3), alpha(4), and alpha(5)). However, an antibody to alpha(8), a more recently iden tified integrin subunit, did precipitate two integrin subunits with el ectrophoretic mobilities in SDS-PAGE identical to alpha(OL) and beta(O L) Functional studies indicated that disruption of oligodendrocyte adh esion to a glial-derived matrix by an RGD-containing synthetic peptide resulted in a substantial decrease in the level of mRNAs for several myelin components including myelin basic protein (MBP), proteolipid pr otein (PLP), and cyclic nucleotide phosphodiesterase (CNP). These resu lts suggest that integrin-mediated adhesion of oligodendrocytes may tr igger signal(s) that induce the expression of myelin genes and thus in fluence oligodendrocyte differentiation.