title: Myosin II is a negative regulator of oligodendrocyte morphological differentiation.
abstract: During their development as myelinating cells, oligodendrocyte progenitors (OPC) undergo dramatic changes in the organization of their cytoskeleton. These changes involve an increase in cell branching and in lamella extension, which is important for the ability of oligodendrocytes to myelinate multiple axons in the CNS. We have previously shown that the levels of the actin-associated motor protein nonmuscle myosin II (NMII) decrease as oligodendrocyte differentiate and that inhibition of NMII activity increases branching and myelination, suggesting that NMII is a negative regulator of oligodendrocyte differentiation. In agreement with this interpretation, we have found that overexpression of NMII prevents oligodendrocyte branching and differentiation and that OPC maturation is accelerated in NMII knockout mice as shown by a significant increase in the percentage of mature MBP(+) cells. Although several pathways have been implicated in oligodendrocyte morphogenesis, their specific contribution to the regulation of NMII activity has not been directly examined. We tested the hypothesis that the activity of NMII in OPC is controlled by Fyn kinase via downregulation of RhoA-ROCK-NMII phosphorylation. We found that treatment with PP2 or knockdown of Fyn using siRNA prevents the decrease in myosin phosphorylation normally observed during OPC differentiation and that the inhibition of branching induced by overexpression of constitutively active RhoA can be reversed by treatment with Y27632 or blebbistatin. Taken together, our results demonstrate that Fyn kinase downregulates NMII activity, thus promoting oligodendrocyte morphological differentiation.
authors.affiliation: Department of Biological Sciences, Hunter College, City University of New York, New York, New York 10065, USA.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rusielewicz
authors.forename: Ambika
authors.initials: A
authors.lastname: Tewari
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Leitman
authors.forename: Steven
authors.initials: S
authors.lastname: Einheber
authors.forename: Carmen V
authors.initials: CV
authors.lastname: Melendez-Vasquez
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron; D024462:Myosin Type II / Q000172:deficiency / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
chemical_list: D051076:Proto-Oncogene Proteins c-fyn; D024462:Myosin Type II