Hasaka Thomas P, Myers Kenneth A, Baas Peter W
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurosci. 2004 Dec 15;24(50):11291-301. doi: 10.1523/JNEUROSCI.3443-04.2004.
Microtubules originate at the centrosome of the neuron and are then released for transport down the axon, in which they can move both anterogradely and retrogradely during axonal growth. It has been hypothesized that these movements occur by force generation against the actin cytoskeleton. To test this, we analyzed the movement, distribution, and orientation of microtubules in neurons pharmacologically depleted of actin filaments. Actin depletion reduced but did not eliminate the anterograde movements and had no effect on the frequency of retrograde movements. Consistent with the idea that microtubules might also move against neighboring microtubules, actin depletion completely inhibited the outward transport of microtubules under experimental conditions of low microtubule density. Interestingly, visualization of microtubule assembly shows that actin depletion actually enhances the tendency of microtubules to align with one another. Such microtubule-microtubule interactions are sufficient to orient microtubules in their characteristic polarity pattern in axons grown overnight in the absence of actin filaments. In fact, microtubule behaviors were only chaotic after actin depletion in peripheral regions of the neuron in which microtubules are normally sparse and hence lack neighboring microtubules with which they could interact. On the basis of these results, we conclude that microtubules are transported against either actin filaments or neighboring microtubules in the anterograde direction but only against other microtubules in the retrograde direction. Moreover, the transport of microtubules against one another provides a surprisingly effective option for the deployment and orientation of microtubules in the absence of actin filaments.
微管起源于神经元的中心体，然后被释放以便沿着轴突运输，在轴突生长过程中它们可以顺行和逆行移动。据推测，这些移动是通过对肌动蛋白细胞骨架产生力而发生的。为了验证这一点，我们分析了在药理学方法去除肌动蛋白丝的神经元中微管的移动、分布和方向。去除肌动蛋白减少了但并未消除顺行移动，并且对逆行移动的频率没有影响。与微管也可能与相邻微管相互作用移动的观点一致，在微管密度低的实验条件下，去除肌动蛋白完全抑制了微管的向外运输。有趣的是，微管组装的可视化显示，去除肌动蛋白实际上增强了微管彼此对齐的趋势。这种微管 - 微管相互作用足以使微管在没有肌动蛋白丝的情况下过夜生长的轴突中以其特征性的极性模式排列。事实上，只有在神经元外周区域去除肌动蛋白后微管行为才变得混乱，在该区域微管通常稀疏，因此缺乏它们可以相互作用的相邻微管。基于这些结果，我们得出结论，微管在顺行方向上是逆着肌动蛋白丝或相邻微管运输的，但在逆行方向上仅逆着其他微管运输。此外，微管相互之间的运输为在没有肌动蛋白丝的情况下微管的部署和定向提供了一个出人意料的有效方式。
