Kinesin-binding protein ensures accurate chromosome segregation by buffering KIF18A and KIF15.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
01 04 2019
01 04 2019
Historique:
received:
27
06
2018
revised:
09
11
2018
accepted:
08
01
2019
pubmed:
3
2
2019
medline:
14
4
2020
entrez:
3
2
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30709852
pii: jcb.201806195
doi: 10.1083/jcb.201806195
pmc: PMC6446846
doi:
Substances chimiques
KIF15 protein, human
0
KIFBP protein, human
0
Nerve Tissue Proteins
0
KIF18A protein, human
EC 3.6.1.-
Kinesins
EC 3.6.4.4
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Video-Audio Media
Langues
eng
Sous-ensembles de citation
IM
Pagination
1218-1234Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM086610
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM121491
Pays : United States
Informations de copyright
© 2019 Malaby et al.
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