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Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK

During mitosis, the nuclear pore complex is disassembled and, increasingly, nucleoporins are proving to have mitotic functions when released from the pore. We find a contribution of the nucleoporin Nup98 to mitotic spindle assembly through regulation of microtubule dynamics. When added to Xenopus ex...

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Detalles Bibliográficos
Autores principales: Cross, Marie K., Powers, Maureen A.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046062/
https://www.ncbi.nlm.nih.gov/pubmed/21209315
http://dx.doi.org/10.1091/mbc.E10-06-0478
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author Cross, Marie K.
Powers, Maureen A.
author_facet Cross, Marie K.
Powers, Maureen A.
author_sort Cross, Marie K.
collection PubMed
description During mitosis, the nuclear pore complex is disassembled and, increasingly, nucleoporins are proving to have mitotic functions when released from the pore. We find a contribution of the nucleoporin Nup98 to mitotic spindle assembly through regulation of microtubule dynamics. When added to Xenopus extract spindle assembly assays, the C-terminal domain of Nup98 stimulates uncontrolled growth of microtubules. Conversely, inhibition or depletion of Nup98 leads to formation of stable monopolar spindles. Spindle bipolarity is restored by addition of purified, recombinant Nup98 C-terminus. The minimal required region of Nup98 corresponds to a portion of the C-terminal domain lacking a previously characterized function. We show association between this region of the C-terminus of Nup98 and both Taxol-stabilized microtubules and the microtubule-depolymerizing mitotic centromere–associated kinesin (MCAK). Importantly, we demonstrate that this domain of Nup98 inhibits MCAK depolymerization activity in vitro. These data support a model in which Nup98 interacts with microtubules and antagonizes MCAK activity, thus promoting bipolar spindle assembly.
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spelling pubmed-30460622011-05-16 Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK Cross, Marie K. Powers, Maureen A. Mol Biol Cell Articles During mitosis, the nuclear pore complex is disassembled and, increasingly, nucleoporins are proving to have mitotic functions when released from the pore. We find a contribution of the nucleoporin Nup98 to mitotic spindle assembly through regulation of microtubule dynamics. When added to Xenopus extract spindle assembly assays, the C-terminal domain of Nup98 stimulates uncontrolled growth of microtubules. Conversely, inhibition or depletion of Nup98 leads to formation of stable monopolar spindles. Spindle bipolarity is restored by addition of purified, recombinant Nup98 C-terminus. The minimal required region of Nup98 corresponds to a portion of the C-terminal domain lacking a previously characterized function. We show association between this region of the C-terminus of Nup98 and both Taxol-stabilized microtubules and the microtubule-depolymerizing mitotic centromere–associated kinesin (MCAK). Importantly, we demonstrate that this domain of Nup98 inhibits MCAK depolymerization activity in vitro. These data support a model in which Nup98 interacts with microtubules and antagonizes MCAK activity, thus promoting bipolar spindle assembly. The American Society for Cell Biology 2011-03-01 /pmc/articles/PMC3046062/ /pubmed/21209315 http://dx.doi.org/10.1091/mbc.E10-06-0478 Text en © 2011 Cross and Powers 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
Cross, Marie K.
Powers, Maureen A.
Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title_full Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title_fullStr Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title_full_unstemmed Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title_short Nup98 regulates bipolar spindle assembly through association with microtubules and opposition of MCAK
title_sort nup98 regulates bipolar spindle assembly through association with microtubules and opposition of mcak
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046062/
https://www.ncbi.nlm.nih.gov/pubmed/21209315
http://dx.doi.org/10.1091/mbc.E10-06-0478
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