Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization.
Effects of kinesin-5 inhibition on dendritic architecture and microtubule organization.
复制标题
DOI：
10.1091/mbc.e14-08-1313
复制
发表时间：
2015-01-01
影响因子：
3.3
通讯作者：
Baas PW
中科院分区：
文献类型：
--
作者：
Kahn OI;Sharma V;González-Billault C;Baas PW
激酶5是一种分子运动蛋白，在有丝分裂中起着重要作用，其抑制对有丝分裂后末期神经元树突的形态和微管组织有显著影响。驱动蛋白-5作为一个制动器，可以限制其他运动蛋白影响微管组织和分布的能力。运动蛋白-5是一种慢速的同四聚体运动蛋白，以其在有丝分裂纺锤体中的重要作用而闻名，它限制了更快的运动蛋白移动微管的速度。在神经元中，实验性抑制kinesin-5通过增加轴突轴内微管的移动性和微管侵入生长锥，使轴突生长更快。驱动蛋白-5在树突中的作用是否不同，因为它们在轴突中没有负端-远端微管？利用培养的啮齿动物原代神经元，我们发现在不同的时间窗口抑制kinesin-5会产生树突形态和微管组织的变化。具体来说，树突变得更短更薄，并且含有更多的负端远端微管，这表明正常作用的激酶-5抑制了向树突运输的负端远端微管的数量。另外的数据表明，在神经元中，CDK5是负责在Thr-926磷酸化激酶，这对于激酶5与微管结合是重要的。我们还发现，激酶5优先与富含酪氨酸化微管蛋白的微管结合。这与观察到的驱动蛋白-5在树突微管上的积累是一致的，因为它们比轴突微管更少去酪氨酸。
Inhibition of kinesin-5, a molecular motor protein best known for its essential role in mitosis, has notable effects on the morphology and microtubule organization of dendrites of terminally postmitotic neurons. Kinesin-5 acts as a brake that can limit the capacity of other motor proteins to influence microtubule organization and distribution. Kinesin-5 is a slow homotetrameric motor protein best known for its essential role in the mitotic spindle, where it limits the rate at which faster motors can move microtubules. In neurons, experimental suppression of kinesin-5 causes the axon to grow faster by increasing the mobility of microtubules in the axonal shaft and the invasion of microtubules into the growth cone. Does kinesin-5 act differently in dendrites, given that they have a population of minus end–distal microtubules not present in axons? Using rodent primary neurons in culture, we found that inhibition of kinesin-5 during various windows of time produces changes in dendritic morphology and microtubule organization. Specifically, dendrites became shorter and thinner and contained a greater proportion of minus end–distal microtubules, suggesting that kinesin-5 acting normally restrains the number of minus end–distal microtubules that are transported into dendrites. Additional data indicate that, in neurons, CDK5 is the kinase responsible for phosphorylating kinesin-5 at Thr-926, which is important for kinesin-5 to associate with microtubules. We also found that kinesin-5 associates preferentially with microtubules rich in tyrosinated tubulin. This is consistent with an observed accumulation of kinesin-5 on dendritic microtubules, as they are known to be less detyrosinated than axonal microtubules.