title: Mitotic regulator SKAP forms a link between kinetochore core complex KMN and dynamic spindle microtubules.
abstract: Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent study shows that mitotic motor CENP-E cooperates with SKAP to orchestrate an accurate chromosome movement in mitosis. However, it remains elusive how kinetochore core microtubule binding activity KMN (KNL1-MIS12-NDC80) regulates microtubule plus-end dynamics. Here, we identify a novel interaction between MIS13 and SKAP that orchestrates accurate interaction between kinetochore and dynamic spindle microtubules. SKAP physically interacts with MIS13 and specifies kinetochore localization of SKAP. Suppression of MIS13 by small interfering RNA abrogates the kinetochore localization of SKAP. Total internal reflection fluorescence microscopic assays demonstrate that SKAP exhibits an EB1-dependent, microtubule plus-end loading and tracking in vitro. Importantly, SKAP is essential for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis. Based on those findings, we reason that SKAP constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division.
authors.affiliation: Anhui Key Laboratory for Cellular Dynamics and University of Science and Technology of China, Hefei 230027, China.
authors.forename: Xiwei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Zhuang
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.forename: Youjun
authors.initials: Y
authors.lastname: Chu
authors.forename: Phil
authors.initials: P
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lifang
authors.initials: L
authors.lastname: Liu
authors.forename: Gregory
authors.initials: G
authors.lastname: Adams
authors.forename: Guowei
authors.initials: G
authors.lastname: Fang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dou
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Yuejia
authors.initials: Y
authors.lastname: Huang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C532764:DSN1 protein, human; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes