Abstract
Differentiation of oligodendrocytes results in the formation of the myelin sheath, a dramatic morphological alteration that accompanies cell specialization. Here, we demonstrate that changes in the extracellular microenvironment may regulate these morphological changes by altering intracellular vesicular trafficking of myelin sheet-directed proteins. The data reveal that fibronectin, in contrast to laminin-2, decreased membrane-directed transport of endogenous NCAM 140 and the model viral protein VSV G, both proteins normally residing in the myelin membrane. The underlying mechanism relies on an integrin-mediated activation of PKC, which causes stable phosphorylation of MARCKS. As a result, dynamic reorganization of the cortical actin cytoskeleton necessary for the targeting of vesicular trafficking to the myelin sheet is precluded, a prerequisite for morphological differentiation. These data are discussed in the context of the demyelinating disease multiple sclerosis, i.e., that leakage of fibronectin across the blood-brain barrier may impede myelination by interference with intracellular myelin sheet-directed membrane transport.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Line
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Cell Membrane / metabolism
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Cytoplasmic Vesicles / metabolism
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Cytoskeleton / metabolism
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Fibronectins / metabolism*
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Fibronectins / pharmacology
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Integrin beta1 / metabolism*
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Intracellular Signaling Peptides and Proteins / metabolism
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Laminin / metabolism
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Laminin / pharmacology
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Membrane Glycoproteins / metabolism
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Membrane Proteins / metabolism
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Myelin Sheath / metabolism
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Myristoylated Alanine-Rich C Kinase Substrate
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Oligodendroglia / cytology
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Oligodendroglia / metabolism*
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Phosphorylation
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Protein Kinase C / metabolism*
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Protein Transport / physiology
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Rats
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Rats, Wistar
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Viral Envelope Proteins / metabolism
Substances
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Cell Adhesion Molecules, Neuronal
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Fibronectins
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G protein, vesicular stomatitis virus
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Integrin beta1
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Intracellular Signaling Peptides and Proteins
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Laminin
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Marcks protein, rat
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Membrane Glycoproteins
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Membrane Proteins
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NCAM140, rat
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Viral Envelope Proteins
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laminin alpha 2
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Myristoylated Alanine-Rich C Kinase Substrate
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Protein Kinase C