Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.
J Neurosci. 2010 Nov 3;30(44):14896-906. doi: 10.1523/JNEUROSCI.3739-10.2010.
Kinesin-12 (also called Kif15) is a mitotic motor protein that continues to be expressed in developing neurons. Depletion of kinesin-12 causes axons to grow faster, more than doubles the frequency of microtubule transport in both directions in the axon, prevents growth cones from turning properly, and enhances the invasion of microtubules into filopodia. These results are remarkably similar to those obtained in previous studies in which neurons were depleted of kinesin-5 (also called Eg5 or Kif11), another mitotic motor protein that continues to be expressed in developing neurons. However, there are also notable differences in the phenotypes obtained with depleting each of these motors. Depleting kinesin-12 decreases axonal branching and growth cone size, whereas inhibiting kinesin-5 increases these parameters. In addition, depleting kinesin-12 diminishes the appearance of growth-cone-like waves along the length of the axon, an effect not observed with depletion of kinesin-5. Finally, depletion of kinesin-12 abolishes the "waggling" behavior of microtubules that occurs as they assemble along actin bundles within filopodia, whereas inhibition of kinesin-5 does not. Interestingly, and perhaps relevant to these differences in phenotype, in biochemical studies, kinesin-12 coimmunoprecipitates with actin but kinesin-5 does not. Collectively, these findings support a scenario whereby kinesin-12 shares functions with kinesin-5 related to microtubule-microtubule interactions, but kinesin-12 has other functions not shared by kinesin-5 that are related to the ability of kinesin-12 to interact with actin.
驱动蛋白-12（也称为 Kif15）是一种有丝分裂驱动蛋白，在发育中的神经元中持续表达。驱动蛋白-12 的耗竭会导致轴突生长得更快，使轴突中微管运输的双向频率增加一倍以上，阻止生长锥正常转向，并增强微管侵入丝状伪足。这些结果与先前的研究结果非常相似，在这些研究中，神经元中耗尽了另一种有丝分裂驱动蛋白——驱动蛋白-5（也称为 Eg5 或 Kif11），该蛋白在发育中的神经元中也持续表达。然而，用这两种马达蛋白中的每一种进行耗竭时，获得的表型也有明显的差异。驱动蛋白-12 的耗竭会减少轴突分支和生长锥的大小，而抑制驱动蛋白-5 则会增加这些参数。此外，驱动蛋白-12 的耗竭会减少轴突上生长锥样波的出现，而用驱动蛋白-5 耗竭则不会观察到这种现象。最后，驱动蛋白-12 的耗竭会消除微管在沿肌动蛋白束组装到丝状伪足过程中发生的“摆动”行为，而抑制驱动蛋白-5 则不会。有趣的是，也许与这些表型差异有关，在生化研究中，驱动蛋白-12 与肌动蛋白共免疫沉淀，但驱动蛋白-5 则没有。综上所述，这些发现支持了这样一种情景，即驱动蛋白-12 与驱动蛋白-5 共享与微管-微管相互作用相关的功能，但驱动蛋白-12 具有驱动蛋白-5 不具有的与驱动蛋白-12 与肌动蛋白相互作用的能力相关的其他功能。
