Coupling Between Microtubule Sliding, Plus-End Growth and Spindle Length Revealed by Kinesin-8 Depletion
Coupling Between Microtubule Sliding, Plus-End Growth and Spindle Length Revealed by Kinesin-8 Depletion
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DOI：
10.1002/cm.20482
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发表时间：
2010-11-01
期刊：
影响因子：
2.9
通讯作者：
Scholey, Jonathan M.
中科院分区：
文献类型：
--
作者：
Wang, Haifeng;Brust-Mascher, Ingrid;Scholey, Jonathan M.
有丝分裂纺锤体长度的控制需要微管（MT）动力学和电机产生的力量之间的协调。为了研究MT加端聚合如何有助于果蝇胚胎纺锤体长度，我们研究了MT加端解聚酶，驱动蛋白-8的动力学，以及使用突变体和抗体显微注射抑制驱动蛋白-8的影响。正如预期的那样，驱动蛋白-8被发现有助于后期A。此外，驱动蛋白-8的缺失导致：（i）极间（ip）MT+末端的过度聚合，其“过度生长”以穿透远端半纺锤体;（ii）与MT+末端聚合相耦合的向极ipMT滑动速率的增加;（iii）在中期/后期A期间纺锤体的过早伸长;和（iv）后期B纺锤体伸长速率的增加，其与MT滑动速率线性相关。这是最好的解释，修订后的“ipMT滑动/负端解聚”模型主轴长度控制，其中包括ipMT加端动态和向外ipMT滑动驱动极通量和主轴伸长之间的耦合。(C)2010 Wiley-Liss，Inc.
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. (C) 2010 Wiley-Liss, Inc.