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Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15

Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement...

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Autores principales: Malaby, Heidi L.H., Dumas, Megan E., Ohi, Ryoma, Stumpff, Jason
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446846/
https://www.ncbi.nlm.nih.gov/pubmed/30709852
http://dx.doi.org/10.1083/jcb.201806195
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author Malaby, Heidi L.H.
Dumas, Megan E.
Ohi, Ryoma
Stumpff, Jason
author_facet Malaby, Heidi L.H.
Dumas, Megan E.
Ohi, Ryoma
Stumpff, Jason
author_sort Malaby, Heidi L.H.
collection PubMed
description Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation.
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spelling pubmed-64468462019-10-01 Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15 Malaby, Heidi L.H. Dumas, Megan E. Ohi, Ryoma Stumpff, Jason J Cell Biol Research Articles Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding. Consistent with these effects, the mitotic localizations of KIF18A and KIF15 are altered by overexpression of KBP. Cells depleted of KBP exhibit lagging chromosomes in anaphase, an effect that is recapitulated by KIF15 and KIF18A overexpression. Based on these data, we propose a model in which KBP acts as a protein buffer in mitosis, protecting cells from excessive KIF18A and KIF15 activity to promote accurate chromosome segregation. Rockefeller University Press 2019-04-01 2019-02-01 /pmc/articles/PMC6446846/ /pubmed/30709852 http://dx.doi.org/10.1083/jcb.201806195 Text en © 2019 Malaby et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/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 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Malaby, Heidi L.H.
Dumas, Megan E.
Ohi, Ryoma
Stumpff, Jason
Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title_full Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title_fullStr Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title_full_unstemmed Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title_short Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15
title_sort kinesin-binding protein ensures accurate chromosome segregation by buffering kif18a and kif15
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446846/
https://www.ncbi.nlm.nih.gov/pubmed/30709852
http://dx.doi.org/10.1083/jcb.201806195
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