Cell Reports
Volume 18, Issue 2, 10 January 2017, Pages 314-323
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Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin

https://doi.org/10.1016/j.celrep.2016.12.053Get rights and content
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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

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.

Keywords

myelin
oligodendrocytes
glia
axons
neurodegeneration
CNP
MBP
demyelinating diseases

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