L. Pedraza et al., THE ACTIVE-TRANSPORT OF MYELIN BASIC-PROTEIN INTO THE NUCLEUS SUGGESTS A REGULATORY ROLE IN MYELINATION, Neuron, 18(4), 1997, pp. 579-589
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.