University of Oulu

Nicolas Snaidero, Caroline Velte, Matti Myllykoski, Arne Raasakka, Alexander Ignatev, Hauke B. Werner, Michelle S. Erwig, Wiebke Möbius, Petri Kursula, Klaus-Armin Nave, Mikael Simons, Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin, Cell Reports, Volume 18, Issue 2, 10 January 2017, Pages 314-323, ISSN 2211-1247, ( Keywords: myelin; oligodendrocytes; glia; axons; neurodegeneration; CNP; MBP; demyelinating diseases

Antagonistic functions of MBP and CNP establish cytosolic channels in CNS myelin

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Author: Snaidero, Nicolas1,2; Velte, Caroline1; Myllykoski, Matti3;
Organizations: 1Cellular Neuroscience, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
2Institute of Neuronal Cell Biology, Technical University Munich, 80805 Munich, Germany
3Faculty of Biochemistry and Molecular Biology and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland
4Department of Biomedicine, University of Bergen, 5009 Bergen, Norway
5Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
6Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany
7German Center for Neurodegenerative Disease (DZNE), 6250 Munich, Germany
8Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 3.9 MB)
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Language: English
Published: Elsevier, 2017
Publish Date: 2017-04-05


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.

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Series: Cell reports
ISSN: 2211-1247
ISSN-E: 2211-1247
ISSN-L: 2211-1247
Volume: 18
Issue: 2
Pages: 314 - 323
DOI: 10.1016/j.celrep.2016.12.053
Type of Publication: A1 Journal article – refereed
Field of Science: 3112 Neurosciences
Funding: This work was supported by an ERC CoG grant (647168) (M.S.) and by grants from the German Research Foundation (SI 746/9-1,10- 1, SPP1757; TRR128, TRR43), the Tschira-Stiftung, ERC advanced grants AxoGLIA and MyeliNANO (to K.-A.N.), the Cluster of Excellence and DFG Research Center CNMBP (W.M. and K.-A.N.) and SyNergy (M.S.), and the Academy of Finland (252066), the Emil Aaltonen Foundation, and the Sigrid Juse ´ lius Foundation (P.K.). Open Access funded by European Research Council.
Academy of Finland Grant Number: 252066
Detailed Information: 252066 (Academy of Finland Funding decision)
Copyright information: © 2016 The Author(s). Under a Creative Commons license