Leo Lanfranco, Yu Wenqian, D'Rozario Mitchell, Waddell Edward A, Marenda Daniel R, Baird Michelle A, Davidson Michael W, Zhou Bin, Wu Bingro, Baker Lisa, Sharp David J, Baas Peter W
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Department of Biology, Drexel University, Philadelphia, PA 19104, USA.
Cell Rep. 2015 Sep 22;12(11):1723-30. doi: 10.1016/j.celrep.2015.08.017. Epub 2015 Sep 3.
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.
轴突中的单个微管（MTs）由高度乙酰化的稳定结构域和未乙酰化的不稳定结构域组成。传统的微管切断蛋白优先切割稳定结构域中的微管。在果蝇中，fidgetin就是以这种方式发挥作用的，靶向敲低会导致神经元轴突中乙酰化（稳定）微管质量的比例更高。相反，在fidgetin基因敲除小鼠中，乙酰化的微管质量比例低于对照动物。当从培养的啮齿动物神经元中去除fidgetin时，轴突微管质量增加62%，且全部为不稳定微管。与此同时，会有更多的小突起和更长的轴突。结合实验数据表明脊椎动物的fidgetin靶向未乙酰化的微管蛋白，这些结果表明脊椎动物的fidgetin（与其果蝇同源物不同）通过抑制微管不稳定结构域的扩展来调节神经元发育。
