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Genes to Cells (2006) 11, 845-857. doi:10.1111/j.1365-2443.2006.00990.x
© 2006 Blackwell Publishing or its licensors

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Mammalian CLASPs are required for mitotic spindle organization and kinetochore alignment

Yuko Mimori-Kiyosue1,*, Ilya Grigoriev2,3, Hiroyuki Sasaki1,4, Chiyuki Matsui1, Anna Akhmanova3, Shoichiro Tsukita5,6 and Ivan Vorobjev7,*

1 KAN Research Institute, Kyoto Research Park, Shimogyo-ku, Kyoto 600-8815, Japan
2 Department of Cell Biology and Histology, Moscow State University, Vorobjevi Gory, Moscow, 119992, Russia
3 MGC Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands
4 Institute of DNA Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
5 Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8315, Japan
6 Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Sakyo-ku, Kyoto 606-8501, Japan
7 Laboratory of Cell Motility, A. N. Belozersky Institute, Moscow State University, Vorobjevi Gory, Moscow, 119992, Russia

CLASP1 and CLASP2 are homologous mammalian proteins, which associate with the ends of growing microtubules, as well as the cell cortex and the kinetochores of mitotic chromosomes. Previous studies have shown that in interphase cells CLASPs can attach microtubule plus ends to the cortex and stabilize them by repeatedly rescuing them from depolymerization. Here we show that CLASP1 and 2 play similar and redundant roles in organizing the mitotic apparatus in HeLa cells. Simultaneous depletion of both CLASPs causes mitotic spindle defects and a significant metaphase delay, which often results in abnormal exit from mitosis. Metaphase delay is associated with decreased kinetochore tension, increased kinetochore oscillations and more rapid microtubule growth. We show that the association of CLASP2 with the kinetochores relies on its C-terminal domain, but is independent of microtubules or association with CLIP-170. We propose that CLASPs exhibit at the kinetochores an activity similar to that at the cortex, providing apparent stabilization of microtubules by locally reducing the amplitude of growth/shortening episodes at the microtubule ends. This local stabilization of microtubules is essential for the formation of normal metaphase spindle, completion of anaphase and cytokinesis.


Communicated by: Shuh Narumiya

* Correspondence: E-mail: y-kiyosue{at}kan.gr.jp; ivorobjev{at}mail.ru




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