Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules.
Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules.
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DOI：
10.1016/j.celrep.2015.08.017
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发表时间：
2015-09-22
期刊：
影响因子：
8.8
通讯作者：
Baas PW
中科院分区：
文献类型：
--
作者：
Leo L;Yu W;D'Rozario M;Waddell EA;Marenda DR;Baird MA;Davidson MW;Zhou B;Wu B;Baker L;Sharp DJ;Baas PW
轴突中的单个微管(MTS)由高度乙酰化的稳定结构域和不稳定的结构域组成。传统的MT切断蛋白优先将MT切割在稳定区域。在果蝇中，fidgetin以这种方式发挥作用，通过定向敲除导致轴突中的神经元具有更高比例的乙酰化(稳定)MT质量。相反，在抖动基因敲除的小鼠中，被乙酰化的MT质量分数低于对照动物。当培养的啮齿动物神经元中的Fidgetin被耗尽时，轴突MT质量增加了62%，所有这些都是不稳定的。随之而来的是更多的小突起和更长的轴突。结合实验数据显示脊椎动物fidgetin针对未乙酰化的微管蛋白，这些结果表明脊椎动物fidgetin(不同于其苍蝇直系物)通过抑制MTS不稳定结构域的扩展来调节神经元的发育。
Individual microtubules (MTs) in the axon consist of a stable domain that is highly acetylated and a labile domain that is not. Traditional MT-severing proteins preferentially cut the MT in the stable domain. In Drosophila, fidgetin behaves in this fashion, with targeted knockdown resulting in neurons with a higher fraction of acetylated (stable) MT mass in their axons. Conversely, in a fidgetin knockout mouse, the fraction of MT mass that is acetylated is lower than in the control animal. When fidgetin is depleted from cultured rodent neurons, there is a 62% increase in axonal MT mass, all of which is labile. Concomitantly, there are more minor processes and a longer axon. Together with experimental data showing that vertebrate fidgetin targets unacetylated tubulin, these results indicate that vertebrate fidgetin (unlike its fly ortholog) regulates neuronal development by tamping back the expansion of the labile domains of MTs.