NUCLEAR TRANSPORT OF MYELIN BASIC-PROTEIN

The multiple myelin basic protein (MBP) isoforms expressed by myelinat ing cells are now known to have different expression patterns, The rel ative abundance of the isoforms containing exon II is greater early in myelinogenesis, whereas in compact myelin the isoforms lacking this e xon are more abundant, Further, the individual MBPs exhibit different intracellular localizations, indicating that the isoforms may not be f unctionally equivalent in myelinating cells, The major MBPs (14 kD and 18.5 kD) have strong affinity for membranes, while on the other hand, the less abundant isoforms (17 kD and 21.5 kD) localize to the nucleu s of young oligodendrocytes, suggesting a regulatory role in the myeli nation program, The same intracellular distribution patterns have been observed when the MBPs are expressed in Hela cells and in shiverer ol igodendrocytes, Thus, the intracellular fate of these proteins seems t o be generally directed through alternative expression of exon II, Fur thermore, the extent of MBPexII entry into the nucleus was found to be directly related to the growth state of host cells. In this paper, we demonstrate that nuclear proteins constitutively expressed by Hela ce lls also exhibit an apparently growth-related nucleo-cytoplasmic distr ibution revealing that MBPexII exhibits the same behavior as bona fide nuclear proteins, Also, to further characterize MBP nuclear transport , we explored various parameters of the translocation of MBP into the nucleus using an in vitro system, This experimental paradigm permits t he uncoupling of synthesis and translocation events; thus, the transpo rt of MBP into cell nuclei can be studied as a function of time, We al so evaluated how changes in temperature as well as energy depletion af fect the in vitro nuclear transport of MBP. (C) 1997 Wiley-Liss, Inc.