Human chromokinesins promote chromosome congression and spindle microtubule dynamics during mitosis

被引：104

作者：

Wandke, Cornelia ^{[1
,2
]}

Barisic, Marin ^{[1
,3
]}

Sigl, Reinhard ^{[1
]}

Rauch, Veronika ^{[1
]}

Wolf, Frank ^{[1
]}

Amaro, Ana C. ^{[2
]}

Tan, Chia H. ^{[2
]}

Pereira, Antonio J. ^{[3
]}

Kutay, Ulrike ^{[2
]}

Maiato, Helder ^{[3
,4
]}

Meraldi, Patrick ^{[2
]}

Geley, Stephan ^{[1
]}

机构：

[1] Innsbruck Med Univ, Bioctr, Div Mol Pathophysiol, A-6020 Innsbruck, Austria

[2] ETH, Inst Biochem, CH-8093 Zurich, Switzerland

[3] Univ Porto, Fac Med, Inst Mol & Cellular Biol, Chromosome Instabil & Dynam Lab, P-4099002 Oporto, Portugal

[4] Univ Porto, Fac Med, Dept Expt Biol, P-4099002 Oporto, Portugal

来源：

JOURNAL OF CELL BIOLOGY | 2012年 / 198卷 / 05期

基金：

奥地利科学基金会; 欧洲研究理事会;

关键词：

KINESIN-LIKE PROTEIN; KINETOCHORE DIRECTIONAL INSTABILITY; MITOTIC SPINDLE; METAPHASE PLATE; MIDZONE FORMATION; YEAST KINESIN-8; MOTOR PROTEINS; HUMAN-CELLS; PTK1; CELLS; IN-VITRO;

D O I：

10.1083/jcb.201110060

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chromokinesins are microtubule plus end directed motor proteins that bind to chromosome arms. In Xenopus egg cell-free extracts, Xkid and Xklp1 are essential for bipolar spindle formation but the functions of the human homologues, hKID (KIF22) and KIF4A, are poorly understood. By using RNAi-mediated protein knockdown in human cells, we find that only co-depletion delayed progression through mitosis in a Mad2-dependent manner. Depletion of hKID caused abnormal chromosome arm orientation, delayed chromosome congression, and sensitized cells to nocodazole. Knockdown of KIF4A increased the number and length of microtubules, altered kinetochore oscillations, and decreased kinetochore microtubule flux. These changes were associated with failures in establishing a tight metaphase plate and an increase in anaphase lagging chromosomes. Co-depletion of both chromokinesins aggravated chromosome attachment failures, which led to mitotic arrest. Thus, hKID and KIF4A contribute independently to the rapid and correct attachment of chromosomes by controlling the positioning of chromosome arms and the dynamics of microtubules, respectively.

引用

页码：847 / 863

页数：17

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