KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle

KIF18A (kinesin-8) is required for mammalian mitotic chromosome alignment. KIF18A confines chromosome movement to the mitotic spindle equator by accumulating at the plus-ends of kinetochore microtubule bundles (K-fibers), where it functions to suppress K-fiber dynamics. It is not understood how the...

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Bibliographic Details
Published in:Life science alliance 2019-02, Vol.2 (1), p.e201800169
Main Authors: Malaby, Heidi Lh, Lessard, Dominique V, Berger, Christopher L, Stumpff, Jason
Format: Article
Language:English
Subjects:
Chromosomes - metabolism
HeLa Cells
Humans
Kinesin - genetics
Kinesin - metabolism
Kinetochores - metabolism
Leupeptins - pharmacology
Metaphase - drug effects
Metaphase - physiology
Microtubules - metabolism
RNA, Small Interfering - genetics
Spindle Apparatus - metabolism
Transfection
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Summary:KIF18A (kinesin-8) is required for mammalian mitotic chromosome alignment. KIF18A confines chromosome movement to the mitotic spindle equator by accumulating at the plus-ends of kinetochore microtubule bundles (K-fibers), where it functions to suppress K-fiber dynamics. It is not understood how the motor accumulates at K-fiber plus-ends, a difficult feat requiring the motor to navigate protein dense microtubule tracks. Our data indicate that KIF18A's relatively long neck linker is required for the motor's accumulation at K-fiber plus-ends. Shorter neck linker (sNL) variants of KIF18A display a deficiency in accumulation at the ends of K-fibers at the center of the spindle. Depletion of K-fiber-binding proteins reduces the KIF18A sNL localization defect, whereas their overexpression reduces wild-type KIF18A's ability to accumulate on this same K-fiber subset. Furthermore, single-molecule assays indicate that KIF18A sNL motors are less proficient in navigating microtubules coated with microtubule-associated proteins. Taken together, these results support a model in which KIF18A's neck linker length permits efficient navigation of obstacles to reach K-fiber ends during mitosis.
ISSN:2575-1077
2575-1077
DOI:10.26508/lsa.201800169