title: TPX2 phosphorylation maintains metaphase spindle length by regulating microtubule flux.
abstract: A steady-state metaphase spindle maintains constant length, although the microtubules undergo intensive dynamics. Tubulin dimers are incorporated at plus ends of spindle microtubules while they are removed from the minus ends, resulting in poleward movement. Such microtubule flux is regulated by the microtubule rescue factors CLASPs at kinetochores and depolymerizing protein Kif2a at the poles, along with other regulators of microtubule dynamics. How microtubule polymerization and depolymerization are coordinated remains unclear. Here we show that TPX2, a microtubule-bundling protein and activator of Aurora A, plays an important role. TPX2 was phosphorylated by Aurora A during mitosis. Its phospho-null mutant caused short metaphase spindles coupled with low microtubule flux rate. Interestingly, phosphorylation of TPX2 regulated its interaction with CLASP1 but not Kif2a. The effect of its mutant in shortening the spindle could be rescued by codepletion of CLASP1 and Kif2a that abolished microtubule flux. Together we propose that Aurora A-dependent TPX2 phosphorylation controls mitotic spindle length through regulating microtubule flux.
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Fu
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Minglei
authors.initials: M
authors.lastname: Bian
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Xin
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Zhaoxuan
authors.initials: Z
authors.lastname: Deng
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Guo
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: The Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking University, Beijing 100871, China The State Key Laboratory of Bio-membrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China zhangcm@pku.edu.cn.
authors.forename: Chuanmao
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008677:Metaphase / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D055503:Protein Multimerization; D008941:Spindle Apparatus / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism; D014981:Xenopus
chemical_list: C497850:CLASP1 protein, human; D018797:Cell Cycle Proteins; C509805:KIF2A protein, human; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human; D014404:Tubulin; C576917:AURKA protein, human; D064096:Aurora Kinase A; D016547:Kinesins