Cancer Research UK Centre, University of Liverpool, Liverpool L3 9TA, England, UK.
J Cell Biol. 2011 Mar 21;192(6):959-68. doi: 10.1083/jcb.201008023. Epub 2011 Mar 14.
Astrin is a mitotic spindle-associated protein required for the correct alignment of all chromosomes at the metaphase plate. Astrin depletion delays chromosome alignment and causes the loss of normal spindle architecture and sister chromatid cohesion before anaphase onset. Here we describe an astrin complex containing kinastrin/SKAP, a novel kinetochore and mitotic spindle protein, and three minor interaction partners: dynein light chain, Plk1, and Sgo2. Kinastrin is the major astrin-interacting protein in mitotic cells, and is required for astrin targeting to microtubule plus ends proximal to the plus tip tracking protein EB1. Cells overexpressing or depleted of kinastrin mislocalize astrin and show the same mitotic defects as astrin-depleted cells. Importantly, astrin fails to localize to and track microtubule plus ends in cells depleted of or overexpressing kinastrin. These findings suggest that microtubule plus end targeting of astrin is required for normal spindle architecture and chromosome alignment, and that perturbations of this pathway result in delayed mitosis and nonphysiological separase activation.
Astrin 是一种有丝分裂纺锤体相关蛋白，对于所有染色体在中期板上的正确排列是必需的。 Astrin 缺失会延迟染色体排列，并在后期开始前导致正常纺锤体结构和姐妹染色单体黏合的丧失。在这里，我们描述了一个 astrin 复合物，其中包含 kinastrin/SKAP，一种新的着丝粒和有丝分裂纺锤体蛋白，以及三个次要的相互作用伙伴：动力蛋白轻链、Plk1 和 Sgo2。在有丝分裂细胞中，kinastrin 是 astrin 的主要相互作用蛋白，并且对于 astrin 靶向到靠近 EB1 追踪蛋白的微管正端是必需的。过表达或耗尽 kinastrin 的细胞会导致 astrin 定位错误，并且表现出与 astrin 耗尽细胞相同的有丝分裂缺陷。重要的是，在耗尽或过表达 kinastrin 的细胞中， astrin 无法定位到微管正端并追踪微管正端。这些发现表明 astrin 的微管正端靶向对于正常的纺锤体结构和染色体排列是必需的，并且该途径的扰动会导致有丝分裂延迟和非生理的 separase 激活。
