title: Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin.
abstract: The myelin sheath is a multilamellar plasma membrane extension of highly specialized glial cells laid down in regularly spaced segments along axons. Recent studies indicate that myelin is metabolically active and capable of communicating with the underlying axon. To be functionally connected to the neuron, oligodendrocytes maintain non-compacted myelin as cytoplasmic nanochannels. Here, we used high-pressure freezing for electron microscopy to study these cytoplasmic regions within myelin close to their native state. We identified 2,'3'-cyclic nucleotide 3'-phosphodiesterase (CNP), an oligodendrocyte-specific protein previously implicated in the maintenance of axonal integrity, as an essential factor in generating and maintaining cytoplasm within the myelin compartment. We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP). Our study provides a molecular and structural framework for understanding how myelin maintains its cytoplasm to function as an active axon-glial unit.
authors.affiliation: Cellular Neuroscience, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Institute of Neuronal Cell Biology, Technical University Munich, 80805 Munich, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Snaidero
authors.affiliation: Cellular Neuroscience, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Velte
authors.affiliation: Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Myllykoski
authors.affiliation: Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland; Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Raasakka
authors.affiliation: Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ignatev
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Hauke B
authors.initials: HB
authors.lastname: Werner
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Erwig
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland; Department of Biomedicine, University of Bergen, 5009 Bergen, Norway.
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.affiliation: Cellular Neuroscience, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Institute of Neuronal Cell Biology, Technical University Munich, 80805 Munich, Germany; German Center for Neurodegenerative Disease (DZNE), 6250 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: msimons@gwdg.de.
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001369:Axons / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism*; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D010641:Phenotype
chemical_list: D004676:Myelin Basic Protein; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase
keywords: CNP; MBP; axons; demyelinating diseases; glia; myelin; neurodegeneration; oligodendrocytes