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Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning

Mitotic spindle positioning specifies the plane of cell division during anaphase. Spindle orientation and positioning are therefore critical to ensure symmetric division in mitosis and asymmetric division during development. The control of astral microtubule length plays an essential role in positio...

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Detalles Bibliográficos
Autores principales: McHugh, Toni, Gluszek, Agata A., Welburn, Julie P.I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028548/
https://www.ncbi.nlm.nih.gov/pubmed/29661912
http://dx.doi.org/10.1083/jcb.201705209
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author McHugh, Toni
Gluszek, Agata A.
Welburn, Julie P.I.
author_facet McHugh, Toni
Gluszek, Agata A.
Welburn, Julie P.I.
author_sort McHugh, Toni
collection PubMed
description Mitotic spindle positioning specifies the plane of cell division during anaphase. Spindle orientation and positioning are therefore critical to ensure symmetric division in mitosis and asymmetric division during development. The control of astral microtubule length plays an essential role in positioning the spindle. In this study, using gene knockout, we show that the kinesin-8 Kif18b controls microtubule length to center the mitotic spindle at metaphase. Using in vitro reconstitution, we reveal that Kif18b is a highly processive plus end–directed motor that uses a C-terminal nonmotor microtubule-binding region to accumulate at growing microtubule plus ends. This region is regulated by phosphorylation to spatially control Kif18b accumulation at plus ends and is essential for Kif18b-dependent spindle positioning and regulation of microtubule length. Finally, we demonstrate that Kif18b shortens microtubules by increasing the catastrophe rate of dynamic microtubules. Overall, our work reveals that Kif18b uses its motile properties to reach microtubule ends, where it regulates astral microtubule length to ensure spindle centering.
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spelling pubmed-60285482018-07-05 Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning McHugh, Toni Gluszek, Agata A. Welburn, Julie P.I. J Cell Biol Research Articles Mitotic spindle positioning specifies the plane of cell division during anaphase. Spindle orientation and positioning are therefore critical to ensure symmetric division in mitosis and asymmetric division during development. The control of astral microtubule length plays an essential role in positioning the spindle. In this study, using gene knockout, we show that the kinesin-8 Kif18b controls microtubule length to center the mitotic spindle at metaphase. Using in vitro reconstitution, we reveal that Kif18b is a highly processive plus end–directed motor that uses a C-terminal nonmotor microtubule-binding region to accumulate at growing microtubule plus ends. This region is regulated by phosphorylation to spatially control Kif18b accumulation at plus ends and is essential for Kif18b-dependent spindle positioning and regulation of microtubule length. Finally, we demonstrate that Kif18b shortens microtubules by increasing the catastrophe rate of dynamic microtubules. Overall, our work reveals that Kif18b uses its motile properties to reach microtubule ends, where it regulates astral microtubule length to ensure spindle centering. Rockefeller University Press 2018-07-02 /pmc/articles/PMC6028548/ /pubmed/29661912 http://dx.doi.org/10.1083/jcb.201705209 Text en © 2018 McHugh et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
McHugh, Toni
Gluszek, Agata A.
Welburn, Julie P.I.
Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title_full Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title_fullStr Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title_full_unstemmed Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title_short Microtubule end tethering of a processive kinesin-8 motor Kif18b is required for spindle positioning
title_sort microtubule end tethering of a processive kinesin-8 motor kif18b is required for spindle positioning
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028548/
https://www.ncbi.nlm.nih.gov/pubmed/29661912
http://dx.doi.org/10.1083/jcb.201705209
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