title: CENP-E kinesin interacts with SKAP protein to orchestrate accurate chromosome segregation in mitosis.
abstract: Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochore. Although previous studies show that the mitotic kinesin CENP-E forms a link between attachment of the spindle microtubule to the kinetochore and the mitotic checkpoint signaling cascade, the molecular mechanism underlying dynamic kinetochore-microtubule interactions in mammalian cells remains elusive. Here, we identify a novel interaction between CENP-E and SKAP that functions synergistically in governing dynamic kinetochore-microtubule interactions. SKAP binds to the C-terminal tail of CENP-E in vitro and is essential for an accurate kinetochore-microtubule attachment in vivo. Immunoelectron microscopic analysis indicates that SKAP is a constituent of the kinetochore corona fibers of mammalian centromeres. Depletion of SKAP or CENP-E by RNA interference results in a dramatic reduction of inter-kinetochore tension, which causes chromosome mis-segregation with a prolonged delay in achieving metaphase alignment. Importantly, SKAP binds to microtubules in vitro, and this interaction is synergized by CENP-E. Based on these findings, we propose that SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation.
authors: Anhui Key Laboratory of Cellular Dynamics and Chemical Biology, University of Science and Technology of China School of Life Sciences, Hefei 230027, China.
authors: Yuejia
authors: Y
authors: Huang
authors: Wenwen
authors: W
authors: Wang
authors: Phil
authors: P
authors: Yao
authors: Xiwei
authors: X
authors: Wang
authors: Xing
authors: X
authors: Liu
authors: Xiaoxuan
authors: X
authors: Zhuang
authors: Feng
authors: F
authors: Yan
authors: Jinhua
authors: J
authors: Zhou
authors: Jian
authors: J
authors: Du
authors: Tarsha
authors: T
authors: Ward
authors: Hanfa
authors: H
authors: Zou
authors: Jiancun
authors: J
authors: Zhang
authors: Guowei
authors: G
authors: Fang
authors: Xia
authors: X
authors: Ding
authors: Zhen
authors: Z
authors: Dou
authors: Xuebiao
authors: X
authors: Yao
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000502:physiology*; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C555984:KNSTRN protein, human; D008869:Microtubule-Associated Proteins; C068688:centromere protein E; D016547:Kinesins