Publication

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.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Ozgen, H., Kahya, N., de Jonge, J. C., Smith, G. S. T., Harauz, G., Hoekstra, D., & Baron, W. (2014). Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms. Biochimica et Biophysica Acta - Molecular Cell Research, 1843(3), 517-530. https://doi.org/10.1016/j.bbamcr.2013.11.026

Author

Ozgen, Hande ; Kahya, Nicoletta ; de Jonge, Jenny C. ; Smith, Graham S. T. ; Harauz, George ; Hoekstra, Dick ; Baron, Wia. / Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2014 ; Vol. 1843, No. 3. pp. 517-530.

Harvard

Ozgen, H, Kahya, N, de Jonge, JC, Smith, GST, Harauz, G, Hoekstra, D & Baron, W 2014, 'Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms', Biochimica et Biophysica Acta - Molecular Cell Research, vol. 1843, no. 3, pp. 517-530. https://doi.org/10.1016/j.bbamcr.2013.11.026

Standard

Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms. / Ozgen, Hande; Kahya, Nicoletta; de Jonge, Jenny C.; Smith, Graham S. T.; Harauz, George; Hoekstra, Dick; Baron, Wia.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1843, No. 3, 03.2014, p. 517-530.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Ozgen H, Kahya N, de Jonge JC, Smith GST, Harauz G, Hoekstra D et al. Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms. Biochimica et Biophysica Acta - Molecular Cell Research. 2014 Mar;1843(3):517-530. https://doi.org/10.1016/j.bbamcr.2013.11.026


BibTeX

@article{be5e14692e964edca4164327367273db,
title = "Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms",
abstract = "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.",
keywords = "Oligodendrocyte, MBP, Nucleocytoplasmic shuttling, Proliferation, MYELIN BASIC-PROTEIN, CENTRAL-NERVOUS-SYSTEM, MOUSE-BRAIN, DEVELOPMENTAL REGULATION, NUCLEAR-LOCALIZATION, BETA-CATENIN, EXPRESSION, OLIGODENDROCYTES, GENE, TRANSPORT",
author = "Hande Ozgen and Nicoletta Kahya and {de Jonge}, {Jenny C.} and Smith, {Graham S. T.} and George Harauz and Dick Hoekstra and Wia Baron",
year = "2014",
month = "3",
doi = "10.1016/j.bbamcr.2013.11.026",
language = "English",
volume = "1843",
pages = "517--530",
journal = "Biochimica et Biophysica Acta - Molecular Cell Research",
issn = "0167-4889",
publisher = "ELSEVIER SCIENCE BV",
number = "3",

}

RIS

TY - JOUR

T1 - Regulation of cell proliferation by nucleocytoplasmic dynamics of postnatal and embryonic exon-II-containing MBP isoforms

AU - Ozgen, Hande

AU - Kahya, Nicoletta

AU - de Jonge, Jenny C.

AU - Smith, Graham S. T.

AU - Harauz, George

AU - Hoekstra, Dick

AU - Baron, Wia

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - Oligodendrocyte

KW - MBP

KW - Nucleocytoplasmic shuttling

KW - Proliferation

KW - MYELIN BASIC-PROTEIN

KW - CENTRAL-NERVOUS-SYSTEM

KW - MOUSE-BRAIN

KW - DEVELOPMENTAL REGULATION

KW - NUCLEAR-LOCALIZATION

KW - BETA-CATENIN

KW - EXPRESSION

KW - OLIGODENDROCYTES

KW - GENE

KW - TRANSPORT

U2 - 10.1016/j.bbamcr.2013.11.026

DO - 10.1016/j.bbamcr.2013.11.026

M3 - Article

C2 - 24321769

VL - 1843

SP - 517

EP - 530

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

SN - 0167-4889

IS - 3

ER -

ID: 14343105