Plk1 Phosphorylates CLIP-170 and Regulates Its Binding to Microtubules for Chromosome Alignment

DOI Web Site PubMed 被引用文献6件 参考文献53件 オープンアクセス
  • Kakeno Mai
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Matsuzawa Kenji
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Matsui Toshinori
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Akita Hiroki
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Sugiyama Ikuko
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Ishidate Fumiyoshi
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Nakano Atsushi
    Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center
  • Takashima Seiji
    Department of Medical Biochemistry, Osaka University Graduate School of Medicine
  • Goto Hidemasa
    Division of Biochemistry, Aichi Cancer Center Research Institute
  • Inagaki Masaki
    Division of Biochemistry, Aichi Cancer Center Research Institute
  • Kaibuchi Kozo
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine
  • Watanabe Takashi
    Department of Cell Pharmacology, Nagoya University Graduate School of Medicine

書誌事項

公開日
2014
資源種別
journal article
DOI
  • 10.1247/csf.14001
公開者
日本細胞生物学会

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説明

The microtubule (MT) cytoskeleton is essential for cellular morphogenesis, cell migration, and cell division. MT organization is primarily mediated by a variety of MT-associated proteins. Among these proteins, plus-end-tracking proteins (+TIPs) are evolutionarily conserved factors that selectively accumulate at growing MT plus ends. Cytoplasmic linker protein (CLIP)-170 is a +TIP that associates with diverse proteins to determine the behavior of MT ends and their linkage to intracellular structures, including mitotic chromosomes. However, how CLIP-170 activity is spatially and temporally controlled is largely unknown. Here, we show that phosphorylation at Ser312 in the third serine-rich region of CLIP-170 is increased during mitosis. Polo-like kinase 1 (Plk1) is responsible for this phosphorylation during the mitotic phase of dividing cells. In vitro analysis using a purified CLIP-170 N-terminal fragment showed that phosphorylation by Plk1 diminishes CLIP-170 binding to the MT ends and lattice without affecting binding to EB3. Furthermore, we demonstrate that during mitosis, stable kinetochore/MT attachment and subsequent chromosome alignment require CLIP-170 and a proper phosphorylation/dephosphorylation cycle at Ser312. We propose that CLIP-170 phosphorylation by Plk1 regulates proper chromosome alignment by modulating the interaction between CLIP-170 and MTs in mitotic cells and that CLIP-170 activity is stringently controlled by its phosphorylation state, which depends on the cellular context.

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