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

• DOI: 10.26508/lsa.201800169
• Publication Date: 2019-01-17T22:19:39Z
• Authors: Heidi LH Malaby; Dominique V Lessard; Christopher L Berger; Jason Stumpff
• Keywords: 0301 basic medicine; Leupeptins; Kinesins; Spindle Apparatus; Transfection; Microtubules; Chromosomes; 03 medical and health sciences; Humans; RNA, Small Interfering; Kinetochores; Research Articles; Metaphase; HeLa Cells

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.