Antagonistic functions of MBP and CNP establish cytosolic channels in CNS myelin
| Autor: | Caroline Velte, Petri Kursula, Klaus-Armin Nave, Alexander Ignatev, Mikael Simons, Arne Raasakka, Nicolas Snaidero, Wiebke Möbius, Michelle S Erwig, Hauke B. Werner, Matti Myllykoski |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Central Nervous System Cytoplasm Proteolipid protein 1 metabolism [Myelin Sheath] glia metabolism [Axons] metabolism [Myelin Basic Protein] Myelin Mice 0302 clinical medicine Cytosol 2' 3'-Cyclic Nucleotide 3'-Phosphodiesterase demyelinating diseases metabolism [Actin Cytoskeleton] Axon lcsh:QH301-705.5 Myelin Sheath biology neurodegeneration ultrastructure [Actin Cytoskeleton] Cell biology Actin Cytoskeleton myelin medicine.anatomical_structure Phenotype Biochemistry metabolism [Central Nervous System] CNP oligodendrocytes axons Cytosolic Channels CNS Myelin General Biochemistry Genetics and Molecular Biology metabolism [Cell Membrane] 2' 3'-Cyclic-nucleotide 3'-phosphodiesterase 03 medical and health sciences Report MBP medicine Animals ddc:610 metabolism [Cytoplasm] Cell Membrane Myelin Basic Protein Actin cytoskeleton metabolism [2' 3'-Cyclic Nucleotide 3'-Phosphodiesterase] Myelin basic protein 030104 developmental biology lcsh:Biology (General) nervous system biology.protein Neuron metabolism [Cytosol] 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 18, Iss 2, Pp 314-323 (2017) Cell reports Cell Reports Cell reports 18(2), 314-323 (2017). doi:10.1016/j.celrep.2016.12.053 |
| DOI: | 10.1016/j.celrep.2016.12.053 |
| Popis: | Summary 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. Graphical Abstract Highlights • Characterization of “cytoplasmic channels” in myelin close to their native state • Antagonistic functions of MBP and CNP in generating cytoplasmic channels • CNP interacts with and bundles actin • Reducing MBP levels rescues axonal pathology in CNP-deficient mice Snaidero et al. provide evidence that a system of cytoplasmic-rich channels is generated in myelin sheaths by the antagonist function of MBP and CNP. The authors suggest that these channels are required to provide trophic support to neurons and maintain functional axon-glial units over a long period of time. |
| Databáze: | OpenAIRE |
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