title: Nuclear transport of myelin basic protein.
abstract: The multiple myelin basic protein (MBP) isoforms expressed by myelinating cells are now known to have different expression patterns. The relative abundance of the isoforms containing exon II is greater early in myelinogenesis, whereas in compact myelin the isoforms lacking this exon are more abundant. Further, the individual MBPs exhibit different intracellular localizations, indicating that the isoforms may not be functionally 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 nucleus of young oligodendrocytes, suggesting a regulatory role in the myelination program. The same intracellular distribution patterns have been observed when the MBPs are expressed in Hela cells and in shiverer oligodendrocytes. Thus, the intracellular fate of these proteins seems to be generally directed through alternative expression of exon II. Furthermore, 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 cells also exhibit an apparently growth-related nucleo-cytoplasmic distribution 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 the uncoupling of synthesis and translocation events; thus, the transport of MBP into cell nuclei can be studied as a function of time. We also evaluated how changes in temperature as well as energy depletion affect the in vitro nuclear transport of MBP.
authors.affiliation: Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA. Pedraza@msvax.mssm.edu
authors.forename: L
authors.initials: L
authors.lastname: Pedraza
mesh_terms: D001692:Biological Transport / Q000502:physiology; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005091:Exons / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D014018:Tissue Distribution; D020931:ran GTP-Binding Protein
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D018840:HSP70 Heat-Shock Proteins; D004676:Myelin Basic Protein; D009687:Nuclear Proteins; C062521:RCC1 protein, human; D020931:ran GTP-Binding Protein