Phosphodiesterase-Ialpha/autotaxin: a counteradhesive protein expressed by oligodendrocytes during onset of myelination

Abstract

The initial stages of central nervous system (CNS) myelination require complex interactions of oligodendrocytes with their surrounding extracellular environment. In the present study, we demonstrate that commencing with active myelination oligodendrocytes express phosphodiesterase-Ialpha/autotaxin [PD-Ialpha/ATX (NPP-2)] as a non-membrane-associated extracellular factor. As such a component of the extracellular environment, PD-Ialpha/ATX has the ability to antagonize the adhesive interactions between oligodendroglial cells and known extracellular matrix (ECM) molecules present in the developing CNS. This counteradhesion requires intracellular signaling through heterotrimeric G proteins on fibronectin substrates and thus represents an active cellular response. Similar counteradhesive effects in other systems have been attributed to the activity of matricellular proteins, which support intermediate stages of cell adhesion thought to facilitate cellular locomotion and remodeling. Thus, the release of PD-Ialpha/ATX may be critically involved in the regulation of the initial stages of myelination, i.e., oligodendrocyte remodeling, via modulation of oligodendrocyte-ECM interactions in a matricellular fashion.