Phosphodieterase-Iα/autotaxin and IFAK phosphorylation during controls cytoskeletal organization myelination

Myelination within the central nervous system (CNS) involves substantial morphogenesis of oligodendrocytes requiring plastic changes in oligodendrocyte-extracellular matrix (ECM) interactions, that is, adhesion. Our previous studies indicated that a regulator of such adhesive plasticity is oligodendrocyte-released phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX). We report here, that PD-Ialpha/ATX's adhesion antagonism is mediated by a protein fragment different from the one that stimulates tumor cell motility. Furthermore, PD-Ialpha/ATX's adhesion-antagonizing fragment causes a reorganized distribution of the focal adhesion components vinculin and paxillin and an integrin-dependent reduction in focal adhesion kinase (FAK) phosphorylation at tyrosine residue 925 (pFAK-925). In vivo, a similar reduction in pFAK-925 occurs at the onset of myelination when PD-Ialpha/ATX expression is significantly upregulated. Most importantly, it can also be induced by the application of exogenous PD-Ialpha/ATX. Our data, therefore, suggest that PD-Ialpha/ATX participates in the regulation of myelination via a novel signaling pathway leading to changes in integrin-dependent focal adhesion assembly and consequently oligodendrocyte-ECM interactions. (C) 2004 Elsevier Inc. All rights reserved.