Protein Kinase C Regulates Process Formation by Oligodendrocytes

Abstract

In multiple sclerosis (MS) and other demyelinating disorders, the oligodendrocytes (OLs) and the myelin that they produce are the targets of various pathological processes. In many cases, the insults are continuous and recurring but despite this, remyelination can occur, as it does in MS although incomplete in its extent (Raine et al., 1981; Ghatak et al., 1989; Prineas et al., 1989, 1993; Raine and Wu, 1993; Bruck et al., 1994). Stimuli to enhance OL formation, maturation or function may improve the remyelinating capacity of OLs. One such strategy may be to promote surviving OLs, or OLs formed from progenitors, to extend their processes which may then subsequently enwrap axons to form myelin. We have been interested in the promotion of process outgrowth from adult OLs, reasoning that process formation is a prerequisite for any OL to successfully remyelinate axons. Furthermore, understanding the mechanisms by which adult OLs recapitulate process outgrowth lends itself to uncovering mechanisms of process extension during developmental myelination, since the extension of cellular processes from the oligodendrocyte soma is an early and critical event in normal myelin formation. OLs in culture have served as useful models for their in vivo counterparts. In vitro, OLs extend multiple processes and the plasma membrane of the cultured OL contains all the major proteins and lipids of myelin (Szuchet, 1987; Vartanian et al., 1992). The emergence of myelin proteins and lipids in vitro, even in the absence of neurons or astrocytes, follows a time course that corresponds to that in vivo (Zeller et al., 1985; Dubois-Dalcq et al., 1986; Zalc et al., 1987). Furthermore, OLs isolated from mutant animals with defective myelination show corresponding abnormalities in vitro (Barlett et al., 1988).