Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics
Human CLASP1 is an outer kinetochore component that regulates spindle microtubule dynamics
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DOI：
10.1016/s0092-8674(03)00465-3
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发表时间：
2003-06-27
期刊：
影响因子：
64.5
通讯作者：
Earnshaw, WC
中科院分区：
文献类型：
--
作者：
Maiato, H;Fairley, EAL;Earnshaw, WC
有丝分裂最有趣的方面之一是动粒抓住微管正端的能力，微管正端积极地获得或失去微管蛋白亚基。在这里，我们表明，CLASP1，微管相关蛋白，优先本地化附近的正端生长的纺锤体微管，也是一个动粒区域，我们称之为外冠的组成部分。缺乏动粒结合结构域的CLASP1的截短形式表现为显性阴性，导致形成高度抗解聚的微管束的径向阵列。显微注射CLASP1特异性抗体抑制微管动力学在动粒和整个纺锤体，导致单极星状体的形成与染色体埋在内部。与微管稳定药物孵育拯救着丝粒协会与微管加结束在周边的紫苑。我们的数据表明，CLASP1所需的着丝粒连接微管表现出正常的动态行为。
One of the most intriguing aspects of mitosis is the ability of kinetochores to hold onto plus ends of microtubules that are actively gaining or losing tubulin subunits. Here, we show that CLASP1, a microtubule-associated protein, localizes preferentially near the plus ends of growing spindle microtubules and is also a component of a kinetochore region that we term the outer corona. A truncated form of CLASP1 lacking the kinetochore binding domain behaves as a dominant negative, leading to the formation of radial arrays of microtubule bundles that are highly resistant to depolymerization. Microinjection of CLASP1-specific antibodies suppresses microtubule dynamics at kinetochores and throughout the spindle, resulting in the formation of monopolar asters with chromosomes buried in the interior. Incubation with microtubule-stabilizing drugs rescues the kinetochore association with microtubule plus ends at the periphery of the asters. Our data suggest that CLASP1 is required at kinetochores for attached microtubules to exhibit normal dynamic behavior.