Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
J Cell Biol. 2011 Jun 27;193(7):1229-44. doi: 10.1083/jcb.201104008. Epub 2011 Jun 20.
In animals, the female meiotic spindle is positioned at the egg cortex in a perpendicular orientation to facilitate the disposal of half of the chromosomes into a polar body. In Caenorhabditis elegans, the metaphase spindle lies parallel to the cortex, dynein is dispersed on the spindle, and the dynein activators ASPM-1 and LIN-5 are concentrated at spindle poles. Anaphase-promoting complex (APC) activation results in dynein accumulation at spindle poles and dynein-dependent rotation of one spindle pole to the cortex, resulting in perpendicular orientation. To test whether the APC initiates spindle rotation through cyclin B-CDK-1 inactivation, separase activation, or degradation of an unknown dynein inhibitor, CDK-1 was inhibited with purvalanol A in metaphase-I-arrested, APC-depleted embryos. CDK-1 inhibition resulted in the accumulation of dynein at spindle poles and dynein-dependent spindle rotation without chromosome separation. These results suggest that CDK-1 blocks rotation by inhibiting dynein association with microtubules and with LIN-5-ASPM-1 at meiotic spindle poles and that the APC promotes spindle rotation by inhibiting CDK-1.
在动物中，雌性减数分裂纺锤体垂直于卵皮层定位，以促进一半染色体被丢弃到极体中。在秀丽隐杆线虫中，中期纺锤体与皮层平行，动力蛋白分散在纺锤体上，动力蛋白激活剂 ASPM-1 和 LIN-5 集中在纺锤体极。有丝分裂促进复合物 (APC) 的激活导致动力蛋白在纺锤体极的积累和依赖动力蛋白的一个纺锤体极向皮层的旋转，从而导致垂直取向。为了测试 APC 是否通过细胞周期蛋白 B-CDK-1 的失活、分离酶的激活或未知的动力蛋白抑制剂的降解来启动纺锤体旋转，在 APC 耗尽的中期-I 阻滞胚胎中用 purvalanol A 抑制 CDK-1。CDK-1 的抑制导致动力蛋白在纺锤体极的积累和依赖动力蛋白的纺锤体旋转，而没有染色体分离。这些结果表明，CDK-1 通过抑制动力蛋白与微管的结合以及与减数分裂纺锤体极上的 LIN-5-ASPM-1 的结合来阻止旋转，而 APC 通过抑制 CDK-1 来促进纺锤体旋转。
