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The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization

Mitotic spindle function is critical for cell division and genomic stability. During anaphase, the elongating spindle physically segregates the sister chromatids. However, the molecular mechanisms that determine the extent of anaphase spindle elongation remain largely unclear. In a screen of yeast m...

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Autores principales: Rizk, Rania S., DiScipio, Katherine A., Proudfoot, Kathleen G., Gupta, Mohan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998799/
https://www.ncbi.nlm.nih.gov/pubmed/24616221
http://dx.doi.org/10.1083/jcb.201312039
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author Rizk, Rania S.
DiScipio, Katherine A.
Proudfoot, Kathleen G.
Gupta, Mohan L.
author_facet Rizk, Rania S.
DiScipio, Katherine A.
Proudfoot, Kathleen G.
Gupta, Mohan L.
author_sort Rizk, Rania S.
collection PubMed
description Mitotic spindle function is critical for cell division and genomic stability. During anaphase, the elongating spindle physically segregates the sister chromatids. However, the molecular mechanisms that determine the extent of anaphase spindle elongation remain largely unclear. In a screen of yeast mutants with altered spindle length, we identified the kinesin-8 Kip3 as essential to scale spindle length with cell size. Kip3 is a multifunctional motor protein with microtubule depolymerase, plus-end motility, and antiparallel sliding activities. Here we demonstrate that the depolymerase activity is indispensable to control spindle length, whereas the motility and sliding activities are not sufficient. Furthermore, the microtubule-destabilizing activity is required to counteract Stu2/XMAP215-mediated microtubule polymerization so that spindle elongation terminates once spindles reach the appropriate final length. Our data support a model where Kip3 directly suppresses spindle microtubule polymerization, limiting midzone length. As a result, sliding forces within the midzone cannot buckle spindle microtubules, which allows the cell boundary to define the extent of spindle elongation.
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spelling pubmed-39987992014-09-17 The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization Rizk, Rania S. DiScipio, Katherine A. Proudfoot, Kathleen G. Gupta, Mohan L. J Cell Biol Research Articles Mitotic spindle function is critical for cell division and genomic stability. During anaphase, the elongating spindle physically segregates the sister chromatids. However, the molecular mechanisms that determine the extent of anaphase spindle elongation remain largely unclear. In a screen of yeast mutants with altered spindle length, we identified the kinesin-8 Kip3 as essential to scale spindle length with cell size. Kip3 is a multifunctional motor protein with microtubule depolymerase, plus-end motility, and antiparallel sliding activities. Here we demonstrate that the depolymerase activity is indispensable to control spindle length, whereas the motility and sliding activities are not sufficient. Furthermore, the microtubule-destabilizing activity is required to counteract Stu2/XMAP215-mediated microtubule polymerization so that spindle elongation terminates once spindles reach the appropriate final length. Our data support a model where Kip3 directly suppresses spindle microtubule polymerization, limiting midzone length. As a result, sliding forces within the midzone cannot buckle spindle microtubules, which allows the cell boundary to define the extent of spindle elongation. The Rockefeller University Press 2014-03-17 /pmc/articles/PMC3998799/ /pubmed/24616221 http://dx.doi.org/10.1083/jcb.201312039 Text en © 2014 Rizk et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Rizk, Rania S.
DiScipio, Katherine A.
Proudfoot, Kathleen G.
Gupta, Mohan L.
The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title_full The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title_fullStr The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title_full_unstemmed The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title_short The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
title_sort kinesin-8 kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998799/
https://www.ncbi.nlm.nih.gov/pubmed/24616221
http://dx.doi.org/10.1083/jcb.201312039
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