Fyn tyrosine kinase participates in the compact myelin sheath formation inthe central nervous system

The cellular mechanisms for spiral wrapping and compaction of myelin sheath s by oligodendrocytes are not known yet. In this study, we examined the rol e of fyn tyrosine kinase, which could be responsible for molecular events d uring the stage of myelination in the CNS. Western blot and immunohistochem ical analyses revealed that fyn-deficient mice have significantly lower lev els of myelin basic protein (MBP), which is required for intracellular memb rane adhesion parts so-called major dense line (MDL) and thought to be esse ntial for the stability of myelin sheath. Electron microscopy verified that the myelin ultrastructure could be used to distinguish fyn-deficient mice from wild-type mice, showing a thin and redundant myelin sheath in the corp us callosum. Further, the electron-dense 'major' line in myelin from the pu rified myelin fractions remained condensed, and myelin compaction was split opened in fyn-deficient mice. To determine whether there was a change in t he microheterogeneity of MBP due to a post-translational event we first inv estigated peptidylarginine deiminase (PAD), which is an enzyme that convert s arginine residues in peptides to citrulline residues. PAD immunoreactivit y was observed both in the myelin from fyn-deficient and wild-type mice. By Western blot analysis we found an increase of the citrullined form of MBP. In addition, MBP from fyn-deficient mice did weakly induce vesicle aggrega tion properties of MBP-mediated adhesion. We concluded that although oligod endrocytes from fyn-deficient mice are able to wrap around the axon, they a re unable to form compact myelin due to decreased MBP level and the presenc e of increased citrullinated MBP, (C) 2000 Published by Elsevier Science Ir eland Ltd and the Japan Neuroscience Society. All rights reserved.