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Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration
The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly fa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967982/ https://www.ncbi.nlm.nih.gov/pubmed/24478460 http://dx.doi.org/10.1091/mbc.E13-08-0506 |
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author | Bernis, Cyril Swift-Taylor, Beth Nord, Matthew Carmona, Sarah Chook, Yuh Min Forbes, Douglass J. |
author_facet | Bernis, Cyril Swift-Taylor, Beth Nord, Matthew Carmona, Sarah Chook, Yuh Min Forbes, Douglass J. |
author_sort | Bernis, Cyril |
collection | PubMed |
description | The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. |
format | Online Article Text |
id | pubmed-3967982 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-39679822014-06-16 Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration Bernis, Cyril Swift-Taylor, Beth Nord, Matthew Carmona, Sarah Chook, Yuh Min Forbes, Douglass J. Mol Biol Cell Articles The nuclear import receptors importin β and transportin play a different role in mitosis: both act phenotypically as spatial regulators to ensure that mitotic spindle, nuclear membrane, and nuclear pore assembly occur exclusively around chromatin. Importin β is known to act by repressing assembly factors in regions distant from chromatin, whereas RanGTP produced on chromatin frees factors from importin β for localized assembly. The mechanism of transportin regulation was unknown. Diametrically opposed models for transportin action are as follows: 1) indirect action by RanGTP sequestration, thus down-regulating release of assembly factors from importin β, and 2) direct action by transportin binding and inhibiting assembly factors. Experiments in Xenopus assembly extracts with M9M, a superaffinity nuclear localization sequence that displaces cargoes bound by transportin, or TLB, a mutant transportin that can bind cargo and RanGTP simultaneously, support direct inhibition. Consistently, simple addition of M9M to mitotic cytosol induces microtubule aster assembly. ELYS and the nucleoporin 107–160 complex, components of mitotic kinetochores and nuclear pores, are blocked from binding to kinetochores in vitro by transportin, a block reversible by M9M. In vivo, 30% of M9M-transfected cells have spindle/cytokinesis defects. We conclude that the cell contains importin β and transportin “global positioning system”or “GPS” pathways that are mechanistically parallel. The American Society for Cell Biology 2014-04-01 /pmc/articles/PMC3967982/ /pubmed/24478460 http://dx.doi.org/10.1091/mbc.E13-08-0506 Text en © 2014 Bernis et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Bernis, Cyril Swift-Taylor, Beth Nord, Matthew Carmona, Sarah Chook, Yuh Min Forbes, Douglass J. Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title | Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title_full | Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title_fullStr | Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title_full_unstemmed | Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title_short | Transportin acts to regulate mitotic assembly events by target binding rather than Ran sequestration |
title_sort | transportin acts to regulate mitotic assembly events by target binding rather than ran sequestration |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967982/ https://www.ncbi.nlm.nih.gov/pubmed/24478460 http://dx.doi.org/10.1091/mbc.E13-08-0506 |
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