title: Microtubule stabilization triggers the plus-end accumulation of Kif18A/kinesin-8.
abstract: The precise control of spindle microtubule (MT) dynamics is essential for chromosome capture and alignment. Kif18A/kinesin-8, an essential regulator of kinetochore MT dynamics, accumulates at its plus-ends in metaphase but not prometaphase cells. The underlying mechanism of time-dependent and kinetochore MT-specific plus-end accumulation of Kif18A is unknown. Here, we examined the factors required for the MT plus-end accumulation of Kif18A. In Eg5 inhibitor-treated cells, Kif18A localized along the MTs in the monopolar spindle and rarely accumulated at their plus-ends, indicating that MT-kinetochore association was not sufficient to induce Kif18A accumulation. In contrast, taxol treatment triggered the rapid MT plus-end accumulation of Kif18A regardless of kinetochore association. Furthermore, Aurora B inhibitor-induced stabilization of the plus-ends of kinetochore MTs promoted the plus-end accumulation of Kif18A. In the absence of Kif18A, treatment with taxol but not Eg5 inhibitor causes highly elongated mitotic MTs, suggesting the importance of plus-end accumulation for the MT length-controlling activity of Kif18A. Taken together, we propose that there is a mutual regulation of kinetochore MT plus-end dynamics and Kif18A accumulation, which may contribute to the highly regulated and ordered changes in kinetochore MT dynamics during chromosome congression and oscillation.
authors: Division of Oncology, Department of Cancer Biology, Institute of Medical Science, The University of Tokyo, Japan.
authors: Natsuko
authors: N
authors: Masuda
authors: Tetsuhiro
authors: T
authors: Shimodaira
authors: Shu-Jen
authors: SJ
authors: Shiu
authors: Noriko
authors: N
authors: Tokai-Nishizumi
authors: Tadashi
authors: T
authors: Yamamoto
authors: Miho
authors: M
authors: Ohsugi
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000502:physiology; D017239:Paclitaxel / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: C470243:KIF11 protein, human; D034741:RNA, Small Interfering; D050257:Tubulin Modulators; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C502735:KIF18A protein, human; D016547:Kinesins; D017239:Paclitaxel