Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching.
Kinesin-12, a mitotic microtubule-associated motor protein, impacts axonal growth, navigation, and branching.
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DOI：
10.1523/jneurosci.3739-10.2010
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发表时间：
2010-11-03
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：
Liu M;Nadar VC;Kozielski F;Kozlowska M;Yu W;Baas PW
驱动蛋白12（也称为Kif 15）是一种有丝分裂运动蛋白，在发育中的神经元中持续表达。驱动蛋白-12的耗尽导致轴突生长更快，使轴突中微管在两个方向上的运输频率增加一倍以上，阻止生长锥正常转动，并增强微管侵入丝状伪足。这些结果与以前的研究中获得的结果非常相似，在以前的研究中，神经元耗尽了驱动蛋白-5（也称为Eg 5或Kif 11），这是另一种在发育中的神经元中继续表达的有丝分裂运动蛋白。然而，也有显着的差异，与耗尽这些电机获得的表型。耗尽驱动蛋白-12减少轴突分支和生长锥的大小，而抑制驱动蛋白-5增加这些参数。此外，耗尽驱动蛋白-12减少了沿轴突长度的生长锥样波沿着的出现，这是耗尽驱动蛋白-5时未观察到的效果。最后，耗尽驱动蛋白-12消除了微管的“摆动”行为，这种行为发生在微管沿着沿着肌动蛋白束在丝状伪足内组装时，而抑制驱动蛋白-5则不然。有趣的是，在生化研究中，驱动蛋白-12与肌动蛋白共免疫沉淀，而驱动蛋白-5则不与肌动蛋白共免疫沉淀，这可能与表型的差异有关。总的来说，这些发现支持这样一种情况，即驱动蛋白-12与驱动蛋白-5共享微管-微管相互作用相关的功能，但驱动蛋白-12具有驱动蛋白-5不共享的其他功能，这些功能与驱动蛋白-12与肌动蛋白相互作用的能力有关。
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 co-immunoprecipitates 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 that kinesin-12 has other functions not shared by kinesin-5 that are related to the ability of kinesin-12 to interact with actin.