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

Cell Structure and Function

Mai Kakeno²  Toshinori Matsui²  Seiji Takashima⁴  Ikuko Sugiyama²  Kenji Matsuzawa²  Takashi Watanabe²  Masaki Inagaki³  Atsushi Nakano¹  Hiroki Akita²  Kozo Kaibuchi²  Hidemasa Goto³  Fumiyoshi Ishidate² 

[1] Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center;Department of Cell Pharmacology, Nagoya University Graduate School of Medicine;Division of Biochemistry, Aichi Cancer Center Research Institute;Department of Medical Biochemistry, Osaka University Graduate School of Medicine

关键词: +TIPs;    CLIP-170;    phosphorylation;    Plk1;    microtubules;   

DOI  :  10.1247/csf.14001

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(54)Cited-By(5)Supplementary materials(3)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.

【 授权许可】

Unknown