title: CaMKIIβ regulates oligodendrocyte maturation and CNS myelination.
abstract: CNS myelination and the maturation of the myelinating cells of the CNS, namely oligodendrocytes, are thought to be regulated by molecular mechanisms controlling the actin cytoskeleton. However, the exact nature of these mechanisms is currently only poorly understood. Here we assessed the role of calcium/calmodulin-dependent kinase type II (CaMKII), in particular CaMKIIβ, in oligodendrocyte maturation and CNS myelination. Using in vitro culture studies, our data demonstrate that CaMKIIβ is critical for the proper morphological maturation of differentiating oligodendrocytes, an aspect of oligodendrocyte maturation that is mediated to a large extent by changes in the cellular cytoskeleton. Furthermore, our data provide evidence for an actin-cytoskeleton-stabilizing role of CaMKIIβ in differentiating oligodendrocytes. Using Camk2b knock-out and Camk2b(A303R) mutant mice, our data revealed an in vivo functional role of CaMKIIβ in regulating myelin thickness that may be mediated by a non-kinase-catalytic activity. Our data point toward a critical role of CaMKIIβ in regulating oligodendrocyte maturation and CNS myelination via an actin-cytoskeleton-regulatory mechanism.
authors.affiliation: Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Waggener
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Dupree
authors.forename: Ype
authors.initials: Y
authors.lastname: Elgersma
authors.forename: Babette
authors.initials: B
authors.lastname: Fuss
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D020868:Gene Silencing; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering / Q000502:physiology; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000199:Actins; D001596:Benzylamines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D034741:RNA, Small Interfering; D013449:Sulfonamides; C072105:KN 93; D000096926:Benzenesulfonamides; C517672:Camk2b protein, mouse