Phosphodiesterase-I alpha/autotaxin controls cytoskeletal organization and FAK phosphorylation during 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-I alpha/autotaxin (PD-I alpha/ATX). We report here, that PD-I alpha/ATX's adhesion antagonism is mediated by a protein fragment different from the one that stimulates tumor cell motility. Furthermore, PD-I alpha/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-I alpha/ATX expression is significantly upregulated. Most importantly, it can also be induced by the application of exogenous PD-I alpha/ATX. Our data, therefore, suggest that PD-I alpha/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.
Fox
Michael A
MA
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Alexander
John K
JK
Afshari
Fatemah S
FS
Colello
Raymond J
RJ
Fuss
Babette
B
D000818:Animals; D002478:Cells, Cultured; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism* / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism* / Q000494:pharmacology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism*; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011755:Pyrophosphatases; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099189:Lysophospholipase D
D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005956:Glucose-6-Phosphate Isomerase; D006023:Glycoproteins; D009097:Multienzyme Complexes; D043264:Phosphodiesterase I; D010727:Phosphoric Diester Hydrolases; D011505:Protein-Tyrosine Kinases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D; C496052:Ptk2 protein, rat