PT - JOURNAL ARTICLE AU - Heidi LH Malaby AU - Dominique V Lessard AU - Christopher L Berger AU - Jason Stumpff TI - KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle AID - 10.26508/lsa.201800169 DP - 2019 Feb 01 TA - Life Science Alliance PG - e201800169 VI - 2 IP - 1 4099 - https://www.life-science-alliance.org/content/2/1/e201800169.short 4100 - https://www.life-science-alliance.org/content/2/1/e201800169.full SO - Life Sci. Alliance2019 Feb 01; 2 AB - 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.