Spindly/CCDC99 Is Required for Efficient Chromosome Congression and Mitotic Checkpoint Regulation

被引:106
作者
Barisic, Marin [1 ]
Sohm, Benedicte [1 ]
Mikolcevic, Petra [1 ]
Wandke, Cornelia [1 ]
Rauch, Veronika [1 ]
Ringer, Thomas [3 ]
Hess, Michael [2 ]
Bonn, Guenther [3 ]
Geley, Stephan [1 ]
机构
[1] Innsbruck Med Univ, Div Mol Pathophysiol, Bioctr, A-6020 Innsbruck, Austria
[2] Innsbruck Med Univ, Div Histol & Embryol, A-6020 Innsbruck, Austria
[3] Leopold Franzens Univ Innsbruck, Inst Analyt Chem & Radiochem, A-6020 Innsbruck, Austria
基金
奥地利科学基金会;
关键词
SPINDLE-ASSEMBLY CHECKPOINT; LIGHT INTERMEDIATE CHAIN; CYTOPLASMIC DYNEIN; CENP-E; MICROTUBULE ATTACHMENT; KINETOCHORE COMPONENT; CHROMOKINESIN KID; MOTOR PROTEINS; MITOSIS; CELLS;
D O I
10.1091/mbc.E09-04-0356
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Spindly recruits a fraction of cytoplasmic dynein to kinetochores for poleward movement of chromosomes and control of mitotic checkpoint signaling. Here we show that human Spindly is a cell cycle-regulated mitotic phosphoprotein that interacts with the Rod/ZW10/Zwilch (RZZ) complex. The kinetochore levels of Spindly are regulated by microtubule attachment and biorientation induced tension. Deletion mutants lacking the N-terminal half of the protein (N Delta 253), or the conserved Spindly box (Delta SB), strongly localized to kinetochores and failed to respond to attachment or tension. In addition, these mutants prevented the removal of the RZZ complex and that of MAD2 from bioriented chromosomes and caused cells to arrest at metaphase, showing that RZZ-Spindly has to be removed from kinetochores to terminate mitotic checkpoint signaling. Depletion of Spindly by RNAi, however, caused cells to arrest in prometaphase because of a delay in microtubule attachment. Surprisingly, this defect was alleviated by codepletion of ZW10. Thus, Spindly is not only required for kinetochore localization of dynein but is a functional component of a mechanism that couples dyneindependent poleward movement of chromosomes to their efficient attachment to microtubules.
引用
收藏
页码:1968 / 1981
页数:14
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