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

In a previous study, we showed that activation of protein kinase C (PKC) pr events oligodendrocyte differentiation at the pro-oligodendrocyte stage. Th e present study was undertaken to identify downstream targets of PKC action in oligodendrocyte progenitor cells. Activation of PKC induced the predomi nant phosphorylation of an 80-kD protein, identified as myristoylated alani ne-rich C-kinase substrate (MARCKS). Upon phosphorylation, MARCKS is transl ocated from the plasma membrane to the cytosol. Furthermore, PKC activation perturbed the organization of the actin cytoskeleton, causing a redistribu tion of actin filaments to the submembranous or cortical actin cytoskeleton . As a consequence, transport of a protein traffic marker, the vesicular st omatitis virus glycoprotein, from the trans-Golgi network to the plasma mem brane becomes perturbed. The effect of disruption of the actin filament net work by cytochalasin D perfectly matched the effect of PKC. These data thus favor the existence of a causal relationship between actin rearrangement a nd docking and/or fusion of proteins to the plasma membrane. Interestingly, neither in control cells nor in PKC-activated cells did another protein tr affic marker, influenza hemagglutinin (HA), reach the cell surface. However , an eminent and specific accumulation of HA just underneath the plasma mem brane became apparent upon PKC activation. Yet, this effect could not be si mulated by cytochalasin D treatment. Therefore, these observations imply th at although MARCKS represents a prominent PKC target site in regulating dif ferentiation, another target involves the differential control of cognate p olarized trafficking pathways, which are apparently operating in oligodendr ocyte progenitor cells. (C) 1999 John Wiley & Sons, Inc.