RhoA-Kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor
RhoA-Kinase and myosin II are required for the maintenance of growth cone polarity and guidance by nerve growth factor
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DOI：
10.1002/neu.20258
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发表时间：
2006-07-01
期刊：
影响因子：
--
通讯作者：
Gallo, Gianluca
中科院分区：
文献类型：
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作者：
Loudon, Robert R.;Silver, Lee D.;Gallo, Gianluca
生长锥是高度极化的动态结构，局限于轴突的尖端。生长锥的极性部分是通过抑制远端轴突轴的扩张活动来维持的，这一过程称为轴突巩固。轴突巩固的机制基础，有助于维持生长锥极性尚不清楚。我们报告说，RhoA激酶（ROCK）或肌球蛋白II的抑制导致不稳定的巩固的远端轴突的证据增加丝状伪足和lamellipodial扩展。此外，当ROCK或肌球蛋白II被抑制时，在生长锥处形成的板状伪足迁移到轴突轴上。EYVP-肌动蛋白在远端轴突的动力学分析表明，ROCK负调节肌动蛋白聚合和自发形成的轴突F-肌动蛋白补丁，后者是一种效果，可归因于ROCK介导的肌球蛋白II的调节的膨胀结构的启动。ROCK或肌球蛋白II的抑制阻止生长锥转向神经生长因子，防止抑制的神经生长因子的来源，导致流产转向反应。这些数据阐明了生长锥极性的机制，提供了证据，巩固的远端轴突是一个组成部分的指导，并确定ROCK作为一个负调节F-肌动蛋白聚合的基础上，在远端轴突的增殖活性。(c)2006年，Wiley期刊。Inc.
Growth cones are highly polarized and dynamic structures confined to the tips of axons. The polarity of growth cones is in part maintained by suppression of protrusive activity from the distal axon shaft, a process termed axon consolidation. The mechanistic basis of axon consolidation that contributes to the maintenance of growth cone polarity is not clear. We report that inhibition of RhoA-kinase (ROCK) or myosin II resulted in unstable consolidation of the distal axon as evidenced by increased filopodial and lamellipodial extension. Furthermore, when ROCK or myosin II was inhibited lamellipodia formed at the growth cone migrated onto the axon shaft. Analysis of EYVP-actin dynamics in the distal axon revealed that ROCK negatively regulates actin polymerization and initiation of protrusive structures from spontaneously formed axonal F-actin patches, the latter being an effect attributable to ROCK-mediated regulation of myosin II. Inhibition of ROCK or myosin II blocked growth cone turning toward NGF by preventing suppression of protrusive activity away from the source of NGF, resulting in aborted turning responses. These data elucidate the mechanism of growth cone polarity, provide evidence that consolidation of the distal axon is a component of guidance, and identify ROCK as a negative regulator of F-actin polymerization underlying protrusive activity in the distal axon. (c) 2006 Wiley Periodicals. Inc.