Phosphorylation of importin-α1 by CDK1-cyclin B1 controls mitotic spindle assembly

Li Guo, Khamsah Suryati Mohd, He Ren, Guangwei Xin, Qing Jiang, Paul R. Clarke (Lead / Corresponding author), Chuanmao Zhang (Lead / Corresponding author)

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Abstract

Importin-α serves as an adaptor linking importin-β to proteins carrying a nuclear localization sequence (NLS). During interphase, this interaction enables nuclear protein import, while in mitosis it regulates spindle assembly factors (SAFs) and controls microtubule nucleation, stabilization and spindle function. Here, we show that human importin-α1 is regulated during the cell cycle and is phosphorylated at two sites (threonine 9 and serine 62) during mitosis by the major mitotic protein kinase CDK1-cyclin B. Mutational analysis indicates that the mitotic phosphorylation of importin-α1 inhibits its binding to importin-β and promotes the release of TPX2 and KIFC1, which are then targeted like importin-β to the spindle. Loss of importin-α1 or expression of a non-phosphorylated mutant of importin-α1 results in the formation of shortened spindles with reduced microtubule density and induces a prolonged metaphase, whereas phosphorylation-mimicking mutants are functional in mitosis. We propose that phosphorylation of importin-α1 is a general mechanism for the spatial and temporal control of mitotic spindle assembly by CDK1-cyclin B1 that acts through the release of SAFs such as TPX2 and KIFC1 from inhibitory complexes that restrict spindle assembly.

Original languageEnglish
Article numberjcs232314
Number of pages12
JournalJournal of Cell Science
Volume132
Issue number18
Early online date21 Aug 2019
DOIs
Publication statusPublished - 23 Sep 2019

Keywords

  • Cell cycle
  • Cyclin-dependent kinase
  • Importin
  • Mitosis
  • Spindle assembly

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