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 function to adhere the cytoplasmic leaflets of the myelin bilayer. During oligodendrocyte maturation prior to compact myelin formation, however, certain MBPs have been observed within the cell body and nucleus. We explored the parameters of the translocation of the exon II-containing MBPs (MBPexII) from the site of synthesis in the cell cytoplasm into the nucleus and in some experiments used GFP as a molecular reporter 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 dependent, and may be regulated by phosphorylation state. Further, MBPexII can direct the entry of macromolecular complexes into cell nuclei, revealing that the exon II peptide segment may provide a nuclear localization signal (NLS), perhaps a novel one, or may induce a conformational change in the full-length protein that exposes a cryptic NLS. The MBPexII are thus very unusual in that they are plasma membrane proteins that are also targeted to the nucleus. In oligodendrocytes and Schwann cells, where the MBPs are naturally expressed, it is likely that karyophilic MBPs subserve a regulatory function in implementing the myelination program.
Pedraza
L
L
Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Fidler
L
L
Staugaitis
S M
SM
Colman
D R
DR
D001693:Biological Transport, Active; D002352:Carrier Proteins / Q000378:metabolism; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004058:Diffusion; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D004676:Myelin Basic Protein / Q000378:metabolism* / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014018:Tissue Distribution
D002352:Carrier Proteins; D004676:Myelin Basic Protein; D013755:Tetradecanoylphorbol Acetate