title: Fibronectin impedes "myelin" sheet-directed flow in oligodendrocytes: a role for a beta 1 integrin-mediated PKC signaling pathway in vesicular trafficking.
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.
authors.affiliation: Department of Membrane Cell Biology, Section Membrane Cell Biology, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sisková
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
authors.forename: Hans
authors.initials: H
authors.lastname: de Vries
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D019012:Integrin beta1 / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D005353:Fibronectins; C028391:G protein, vesicular stomatitis virus; D019012:Integrin beta1; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; C000619712:Marcks protein, rat; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C507071:NCAM140, rat; D014759:Viral Envelope Proteins; C102645:laminin alpha 2; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C