Mitotic motors coregulate microtubule patterns in axons and dendrites.
Mitotic motors coregulate microtubule patterns in axons and dendrites.
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有丝分裂运动共同调节轴突和树突中的微管模式
DOI：
10.1523/jneurosci.3070-12.2012
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发表时间：
2012-10-03
期刊：
影响因子：
--
通讯作者：
Baas PW
中科院分区：
文献类型：
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作者：
Lin S;Liu M;Mozgova OI;Yu W;Baas PW
在脊椎动物神经元的轴突中，微管的取向几乎是均匀的，但在树突中，微管的取向是不均匀的。到目前为止的研究提出了一种建立这些微管模式的方案，即微管被运输到轴突和具有正端引导的新生树突中，然后相反方向的额外微管被运输到发育中的树突中。在这里，我们使用现代工具证实，大鼠交感神经元中Kinesin-6(也称为CHO1/MKLP1或KIF23)的耗尽会导致发育中的树突中负末端微管的出现减少，这反过来又会导致树突呈现轴突样的形态。有趣的是，当我们耗尽kinesin-12(也称为kif15或HKLP2)时，我们观察到了类似的现象。这两个马达都以参与其他类型细胞的有丝分裂而闻名，而且都富含在神经元的细胞体和树突中。与遍布神经元的Kinesin-12不同，Kinesin-6在轴突中几乎检测不到。因此，与动蛋白-12的耗尽不同，动蛋白-6的耗竭不会对轴突分支或导航产生影响。有趣的是，任一种运动的耗尽都会导致轴突生长更快，可移动的微管数量也更多。基于这些观察，我们假设了一个模型，在这个模型中，这两个马达产生的力可以减弱从细胞体到轴突的带有正端的微管的运输。这些微管中的一些不仅被阻止进入轴突，而且被负端驱动进入发育中的树突。通过这种方式，这些所谓的“有丝分裂”马达共同调节轴突和树突的微管模式。
Microtubules are nearly uniformly oriented in the axons of vertebrate neurons but are non-uniformly oriented in their dendrites. Studies to date suggest a scenario for establishing these microtubule patterns whereby microtubules are transported into the axon and nascent dendrites with plus-ends-leading, and then additional microtubules of the opposite orientation are transported into the developing dendrites. Here, we used contemporary tools to confirm that depletion of kinesin-6 (also called CHO1/MKLP1 or kif23) from rat sympathetic neurons causes a reduction in the appearance of minus-end-distal microtubules in developing dendrites, which in turn causes them to assume an axon-like morphology. Interestingly, we observed a similar phenomenon when we depleted kinesin-12 (also called kif15 or HKLP2). Both motors are best known for their participation in mitosis in other cell types, and both are enriched in the cell body and dendrites of neurons. Unlike kinesin-12, which is present throughout the neuron, kinesin-6 is barely detectable in the axon. Accordingly, depletion of kinesin-6, unlike depletion of kinesin-12, has no effect on axonal branching or navigation. Interestingly, depletion of either motor results in faster growing axons with greater numbers of mobile microtubules. Based on these observations, we posit a model whereby these two motors generate forces that attenuate the transport of microtubules with plus-ends-leading from the cell body into the axon. Some of these microtubules are not only prevented from moving into the axon but are driven with minus-ends-leading into developing dendrites. In this manner, these so-called “mitotic” motors coregulate the microtubule patterns of axons and dendrites.