NuMA recruits dynein activity to microtubule minus-ends at mitosis
NuMA recruits dynein activity to microtubule minus-ends at mitosis
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DOI：
10.7554/elife.29328
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发表时间：
2017-11-29
期刊：
影响因子：
7.7
通讯作者：
Dumont, Sophie
中科院分区：
文献类型：
--
作者：
Hueschen, Christina L.;Kenny, Samuel J.;Dumont, Sophie
为了在有丝分裂时形成纺锤体，马达对微管施加空间调节的力。我们知道动力蛋白牵拉哺乳动物纺锤体微管的负端，并且预测这种末端的局部活动允许动力蛋白将微管聚集成极点。动力蛋白是如何在负端富集的尚不清楚。在这里，我们使用定量成像和激光消融来显示NuMA将动力蛋白靶向到负端，将动力蛋白活性定位在那里。NuMA被招募到新的负端独立于动力蛋白，比动力蛋白更快；NuMA和dynactin都在负端显示出特定的稳态结合。NuMA向负端定位涉及NuMA规范微管结合域外的c端区域，并且独立于负端结合物γ - turc， CAMSAP1和kansl /3。NuMA的负端结合和动力蛋白-动力蛋白结合模块都需要拯救聚焦的双极纺锤体组织。因此，NuMA可能作为有丝分裂特异性负端货物适配器，靶向动力蛋白活性到负端，将纺锤体微管聚集成极点。
To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin; both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends involves a C-terminal region outside NuMA's canonical microtubule-binding domain and is independent of minus-end binders gamma-TuRC, CAMSAP1, and KANSL1/3. Both NuMA's minus-end binding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles.