Clathrin recruits phosphorylated TACC3 to spindle poles for bipolar spindle assembly and chromosome alignment

Wenxiang Fu, Wei Tao, Puwei Zheng, Jingyan Fu, Minglei Bian, Qing Jiang, Paul R. Clarke, Chuanmao Zhang

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    Abstract

    Transforming acidic coiled-coil-containing protein 3 (TACC3) has been implicated in mitotic spindle assembly, although the mechanisms involved are largely unknown. Here we identify that clathrin heavy chain (CHC) binds specifically to phosphorylated TACC3 and recruits it to spindle poles for proper spindle assembly and chromosome alignment. Phosphorylation of Xenopus TACC3 at serine 620 (S620) and S626, but not S33, is required for its binding with CHC. Knockdown of CHC by RNA interference (RNAi) abolishes the targeting of TACC3 to spindle poles and results in abnormal spindle assembly and chromosome misalignment, similar to the defects caused by TACC3 knockdown. Furthermore, the binding of CHC with phosphorylated TACC3 is inhibited by importin. and this inhibition is reversed by the presence of the GTP-binding nuclear protein Ran in the GTP-bound state. Together, these results indicate that the recruitment of phosphorylated TACC3 to spindle poles by CHC ensures proper spindle assembly and chromosome alignment, and is regulated by Ran.

    Original languageEnglish
    Pages (from-to)3645-3651
    Number of pages7
    JournalJournal of Cell Science
    Volume123
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 2010

    Keywords

    • TACC3
    • Clathrin
    • Phosphorylation
    • Spindle assembly
    • Chromosome alignment
    • LAEVIS EGG EXTRACTS
    • MITOTIC SPINDLE
    • MEDIATED ENDOCYTOSIS
    • AURORA-A
    • PROTEIN
    • MASKIN
    • RCC1
    • RAN
    • MITOSIS
    • FAMILY

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