title: Mitotic Protein CSPP1 Interacts with CENP-H Protein to Coordinate Accurate Chromosome Oscillation in Mitosis.
abstract: Mitotic chromosome segregation is orchestrated by the dynamic interaction of spindle microtubules with the kinetochores. During chromosome alignment, kinetochore-bound microtubules undergo dynamic cycles between growth and shrinkage, leading to an oscillatory movement of chromosomes along the spindle axis. Although kinetochore protein CENP-H serves as a molecular control of kinetochore-microtubule dynamics, the mechanistic link between CENP-H and kinetochore microtubules (kMT) has remained less characterized. Here, we show that CSPP1 is a kinetochore protein essential for accurate chromosome movements in mitosis. CSPP1 binds to CENP-H in vitro and in vivo. Suppression of CSPP1 perturbs proper mitotic progression and compromises the satisfaction of spindle assembly checkpoint. In addition, chromosome oscillation is greatly attenuated in CSPP1-depleted cells, similar to what was observed in the CENP-H-depleted cells. Importantly, CSPP1 depletion enhances velocity of kinetochore movement, and overexpression of CSPP1 decreases the speed, suggesting that CSPP1 promotes kMT stability during cell division. Specific perturbation of CENP-H/CSPP1 interaction using a membrane-permeable competing peptide resulted in a transient mitotic arrest and chromosome segregation defect. Based on these findings, we propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kMT dynamics for accurate chromosome segregation.
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China; the Morehouse School of Medicine and Atlanta Cardiovascular Research Institute, Atlanta, Georgia 30310.
authors.forename: Zhikai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China; the Morehouse School of Medicine and Atlanta Cardiovascular Research Institute, Atlanta, Georgia 30310,; the Airforce General Hospital, Beijing 100036, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Wang
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China; the Airforce General Hospital, Beijing 100036, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Hua
authors.affiliation: the Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Zeqi
authors.initials: Z
authors.lastname: Su
authors.affiliation: the Morehouse School of Medicine and Atlanta Cardiovascular Research Institute, Atlanta, Georgia 30310.
authors.forename: Larry
authors.initials: L
authors.lastname: Brako
authors.affiliation: the Morehouse School of Medicine and Atlanta Cardiovascular Research Institute, Atlanta, Georgia 30310.
authors.forename: Minerva
authors.initials: M
authors.lastname: Garcia-Barrio
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Ye
authors.affiliation: the Airforce General Hospital, Beijing 100036, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wei
authors.affiliation: the National Chromatographic Research and Analysis Center, Chinese Academy of Sciences, Dalian 116023, China.
authors.forename: Hanfa
authors.initials: H
authors.lastname: Zou
authors.affiliation: the Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.affiliation: the Airforce General Hospital, Beijing 100036, China. Electronic address: lfliubj@hotmail.com.
authors.forename: Lifang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China; the Morehouse School of Medicine and Atlanta Cardiovascular Research Institute, Atlanta, Georgia 30310,. Electronic address: xing1017@ustc.edu.cn.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory for Cellular Dynamics, University of Science and Technology of China, Hefei 230027, China. Electronic address: yaoxb@ustc.edu.cn.
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C121933:CENPH protein, human; C514207:CSPP1 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: kinase; kinetochore; microtubule; microtubule-associated protein (MAP); mitosis; mitotic spindle; phosphorylation