Department of Molecular and Cell Biology, One Shields Avenue, University of California Davis, Davis, California 95616, USA.
Cytoskeleton (Hoboken). 2010 Nov;67(11):715-28. doi: 10.1002/cm.20482.
Mitotic spindle length control requires coordination between microtubule (MT) dynamics and motor-generated forces. To investigate how MT plus-end polymerization contributes to spindle length in Drosophila embryos, we studied the dynamics of the MT plus-end depolymerase, kinesin-8, and the effects of kinesin-8 inhibition using mutants and antibody microinjection. As expected, kinesin-8 was found to contribute to anaphase A. Furthermore, kinesin-8 depletion caused: (i) excessive polymerization of interpolar (ip) MT plus ends, which "overgrow" to penetrate distal half spindles; (ii) an increase in the poleward ipMT sliding rate that is coupled to MT plus-end polymerization; (iii) premature spindle elongation during metaphase/anaphase A; and (iv) an increase in the anaphase B spindle elongation rate which correlates linearly with the MT sliding rate. This is best explained by a revised "ipMT sliding/minus-end depolymerization" model for spindle length control which incorporates a coupling between ipMT plus end dynamics and the outward ipMT sliding that drives poleward flux and spindle elongation.
有丝分裂纺锤体长度的控制需要协调微管（MT）动力学和马达产生的力。为了研究 MT 正极聚合如何在果蝇胚胎中促进纺锤体长度，我们研究了 MT 正极去聚合酶，驱动蛋白-8 的动力学以及使用突变体和抗体显微注射的驱动蛋白-8 抑制的效果。正如预期的那样，发现驱动蛋白-8 有助于后期 A。此外，驱动蛋白-8 的耗竭导致：（i）极间（ip）MT 正极的过度聚合，其“过度生长”以穿透远端半纺锤体; （ii）与 MT 正极聚合偶联的 ipMT 向极滑动速率增加; （iii）中期/后期 A 期间过早的纺锤体伸长; 和（iv）后期 B 纺锤体伸长速率增加，其与 MT 滑动速率呈线性相关。这可以通过一个经过修订的“ipMT 滑动/负端去聚合”模型来最好地解释，该模型包含了 ipMT 正极动力学和向外的 ipMT 滑动之间的耦合，该滑动驱动极向通量和纺锤体伸长。
