THE ACTIVE-TRANSPORT OF MYELIN BASIC-PROTEIN INTO THE NUCLEUS SUGGESTS A REGULATORY ROLE IN MYELINATION

The myelin basic proteins (MBPs) are a set of membrane proteins that f unction to adhere the cytoplasmic leaflets of the myelin bilayer. Duri ng oligodendrocyte maturation prior to compact myelin formation, howev er, certain MBPs have been observed within the cell body and nucleus. We explored the parameters of the translocation of the exon II-contain ing MBPs (MBPexII) from the site of synthesis in the cell cytoplasm in to the nucleus and in some experiments used GFP as a molecular reporte r to monitor the intracellular distribution of MBP-GFP fusion proteins in living cells. We show here that the transport of MBPexII into cell nuclei is an active process, which is temperature and energy dependen t, and may be regulated by phosphorylation state. Further, MBPexII can direct the entry of macromolecular complexes into cell nuclei, reveal ing that the exon II peptide segment may provide a nuclear localizatio n signal (NLS), perhaps a novel one, or may induce a conformational ch ange in the full-length protein that exposes a cryptic NLS. The MBPexI I are thus very unusual in that they are plasma membrane proteins that are also targeted to the nucleus. In oligodendrocytes and Schwann cel ls, where the MBPs are naturally expressed, it is likely that karyophi lic MBPs subserve a regulatory function in implementing the myelinatio n program.