Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurosci. 2012 Oct 3;32(40):14033-49. doi: 10.1523/JNEUROSCI.3070-12.2012.
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.
微管在脊椎动物神经元的轴突中几乎是均匀取向的，但在树突中是非均匀取向的。迄今为止的研究表明了一种建立这些微管模式的方案，即微管被正向运输到轴突和新生树突中，然后相反取向的额外微管被运输到正在发育的树突中。在这里，我们使用现代工具证实，从小鼠交感神经元中耗尽驱动蛋白-6（也称为 CHO1/MKLP1 或 kif23）会导致发育中的树突中负端远侧微管的出现减少，这反过来又使它们呈现出类似于轴突的形态。有趣的是，当我们耗尽驱动蛋白-12（也称为 kif15 或 HKLP2）时，我们观察到了类似的现象。这两种马达最著名的是它们在其他细胞类型的有丝分裂中的参与，并且在神经元的细胞体和树突中都很丰富。与存在于整个神经元中的驱动蛋白-12 不同，驱动蛋白-6在轴突中几乎检测不到。因此，与驱动蛋白-12 不同，耗尽驱动蛋白-6对轴突分支或导航没有影响。有趣的是，耗尽这两种马达中的任何一种都会导致具有更多可移动微管的生长更快的轴突。基于这些观察结果，我们提出了一个模型，即这两种马达产生的力会减弱正向运输带有正端的微管从细胞体进入轴突的运输。其中一些微管不仅被阻止进入轴突，而且还被负端驱动进入正在发育的树突。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。
