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Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms

Ozgen, H., Kahya, N., de Jonge, J. C., Smith, G. S. T., Harauz, G., Hoekstra, D. & Baron, W., Mar-2014, In : Biochimica et Biophysica Acta - Molecular Cell Research. 1843, 3, p. 517-530 14 p.

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The only known structural protein required for formation of myelin, produced by oligodendrocytes in the central nervous system, is myelin basic protein (MBP). This peripheral membrane protein has different developmentally-regulated isoforms, generated by alternative splicing. The isoforms are targeted to distinct subcellular locations, which is governed by the presence or absence of exon-Il, although their functional expression is often less clear. Here, we investigated the role of exon-Il-containing MBP isoforms and their link with cell proliferation. Live-cell imaging and FRAP analysis revealed a dynamic nucleocytoplasmic translocation of the exon-II-containing postnatal 21.5-kDa MBP isoform upon mitogenic modulation. Its nuclear export was blocked upon treatment with leptomycin B, an inhibitor of nuclear protein export. Next to the postnatal MBP isoforms, embryonic exon-II-containing MBP (e-MBP) is expressed in primary (immature) oligodendrocytes. The e-MBP isoform is exclusively present in OLN-93 cells, a rat-derived oligodendrocyte progenitor cell line, and interestingly, also in several non-CNS cell lines. As seen for postnatal MBPs, a similar nucleocytoplasmic translocation upon mitogenic modulation was observed for e-MBP. Thus, upon serum deprivation, e-MBP was excluded from the nucleus, whereas re-addition of serum re-established its nuclear localization, with a concomitant increase in proliferation. Knockdown of MBP by shRNA confirmed a role for e-MBP in OLN-93 proliferation, whereas the absence of e-MBP similarly reduced the proliferative capacity of non-CNS cell lines. Thus, exon-Il-containing MBP isoforms may regulate cell proliferation via a mechanism that relies on their dynamic nuclear import and export, which is not restricted to the oligodendrocyte lineage.

Original languageEnglish
Pages (from-to)517-530
Number of pages14
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number3
Publication statusPublished - Mar-2014

    Keywords

  • Oligodendrocyte, MBP, Nucleocytoplasmic shuttling, Proliferation, MYELIN BASIC-PROTEIN, CENTRAL-NERVOUS-SYSTEM, MOUSE-BRAIN, DEVELOPMENTAL REGULATION, NUCLEAR-LOCALIZATION, BETA-CATENIN, EXPRESSION, OLIGODENDROCYTES, GENE, TRANSPORT

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