Protein kinase C prevents oligodendrocyte differentiation: Modulation of actin cytoskeleton and cognate polarized membrane traffic

W Baron, EJ de Vries, H de Vries, D Hoekstra*

*Corresponding author for this work

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30 Citations (Scopus)

Abstract

In a previous study, we showed that activation of protein kinase C (PKC) prevents oligodendrocyte differentiation at the pro-oligodendrocyte stage. The present study was undertaken to identify downstream targets of PKC action in oligodendrocyte progenitor cells. Activation of PKC induced the predominant phosphorylation of an 80-kD protein, identified as myristoylated alanine-rich C-kinase substrate (MARCKS). Upon phosphorylation, MARCKS is translocated from the plasma membrane to the cytosol. Furthermore, PKC activation perturbed the organization of the actin cytoskeleton, causing a redistribution of actin filaments to the submembranous or cortical actin cytoskeleton. As a consequence, transport of a protein traffic marker, the vesicular stomatitis virus glycoprotein, from the trans-Golgi network to the plasma membrane becomes perturbed. The effect of disruption of the actin filament network by cytochalasin D perfectly matched the effect of PKC. These data thus favor the existence of a causal relationship between actin rearrangement and docking and/or fusion of proteins to the plasma membrane. Interestingly, neither in control cells nor in PKC-activated cells did another protein traffic marker, influenza hemagglutinin (HA), reach the cell surface. However, an eminent and specific accumulation of HA just underneath the plasma membrane became apparent upon PKC activation. Yet, this effect could not be simulated by cytochalasin D treatment. Therefore, these observations imply that although MARCKS represents a prominent PKC target site in regulating differentiation, another target involves the differential control of cognate polarized trafficking pathways, which are apparently operating in oligodendrocyte progenitor cells. (C) 1999 John Wiley & Sons, Inc.

Original languageEnglish
Pages (from-to)385-398
Number of pages14
JournalJournal of Neurobiology
Volume41
Issue number3
Publication statusPublished - 15-Nov-1999

Keywords

  • oligodendrocyte differentiation
  • protein kinase C
  • MARCKS
  • actin cytoskeleton
  • membrane flow
  • cognate polarity
  • MYRISTOYL-ELECTROSTATIC SWITCH
  • CULTURED OLIGODENDROCYTES
  • RAT OLIGODENDROCYTES
  • CELLULAR SUBSTRATE
  • PLASMA-MEMBRANE
  • GOLGI-APPARATUS
  • MARCKS PROTEIN
  • GROWTH-FACTOR
  • CELLS
  • PHOSPHORYLATION

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