Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation.
Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation.
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DOI：
10.1091/mbc.e09-04-0356
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发表时间：
2010-06-15
影响因子：
3.3
通讯作者：
Geley S
中科院分区：
文献类型：
--
作者：
Barisic M;Sohm B;Mikolcevic P;Wandke C;Rauch V;Ringer T;Hess M;Bonn G;Geley S
人纺锤体是细胞质动力蛋白的动粒定位所必需的，这对于染色体的向极运动和动粒蛋白流是必需的。此外，Spindly控制RZZ复合物的活性和动粒丰度，这有助于微管附着和有丝分裂检查点活性。纺锤体将细胞质动力蛋白的一部分募集到着丝粒中，用于染色体的向极运动和有丝分裂检查点信号的控制。在这里，我们表明，人类Spindly是一种细胞周期调节的有丝分裂磷蛋白，与杆/ZW 10/Zwilch（RZZ）复合物相互作用。Spindly的动粒水平受微管附着和双向诱导张力的调节。缺失N-末端一半蛋白质（NΔ253）或保守的纺锤体盒（ΔSB）的缺失突变体强烈定位于着丝粒，并且不能对附着或张力做出反应。此外，这些突变体阻止了RZZ复合物和MAD 2从双向染色体上的去除，并导致细胞在中期停滞，这表明RZZ-Spindly必须从动粒中去除以终止有丝分裂检查点信号传导。然而，通过RNAi消耗Spindly，由于微管附着的延迟，导致细胞在前中期停滞。令人惊讶的是，ZW 10的编码减轻了这一缺陷。因此，纺锤体不仅是动力蛋白的动粒定位所需的，而且是将动力蛋白依赖的染色体向极运动与其与微管的有效附着相结合的机制的功能组分。
Human Spindly is required for kinetochore localization of cytoplasmic dynein, which is essential for poleward movement of chromosomes and for kinetochore protein streaming. In addition, Spindly controls the activity and kinetochore abundance of the RZZ complex, which contributes to microtubule attachment and mitotic checkpoint activity. 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 (NΔ253), or the conserved Spindly box (ΔSB), 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 dynein-dependent poleward movement of chromosomes to their efficient attachment to microtubules.
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DOI：
10.1083/jcb.138.3.629
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Carminati JL;Stearns T
通讯作者：
Stearns T
影响因子：
64.8
作者：
Heald, R;Tournebize, R;Karsenti, E
通讯作者：
Karsenti, E
影响因子：
11.4
作者：
Draviam, V. M.;Shapiro, I.;Sorger, P. K.
通讯作者：
Sorger, P. K.
DOI：
10.1038/nrm2804
发表时间：
2009-12
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1083/jcb.153.1.137
发表时间：
2001-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Geley S;Kramer E;Gieffers C;Gannon J;Peters JM;Hunt T
通讯作者：
Hunt T