PDF(Pubmed)
Abstract：
The location of the axon initial segment (AIS) at the junction between the soma and axon of neurons makes it instrumental in maintaining neural polarity and as the site for action potential generation. The AIS is also capable of large-scale relocation in an activity-dependent manner. This represents a form of homeostatic plasticity in which neurons regulate their own excitability by changing the size and/or position of the AIS. While AIS plasticity is important for proper functionality of AIS-containing neurons, the cellular and molecular mechanisms of AIS plasticity are poorly understood. Here, we analyzed changes in the AIS actin cytoskeleton during AIS plasticity using 3D structured illumination microscopy (3D-SIM). We showed that the number of longitudinal actin fibers increased transiently 3 h after plasticity induction. We further showed that actin polymerization, especially formin mediated actin polymerization, is required for AIS plasticity and formation of longitudinal actin fibers. From the formin family of proteins, Daam1 localized to the ends of longitudinal actin fibers. These results indicate that active re-organization of the actin cytoskeleton is required for proper AIS plasticity.
摘要：
轴突初始节段（AIS）在神经元的体细胞和轴突之间的交界处的位置使其有助于维持神经极性并作为动作电位产生的部位。AIS还能够以依赖于活动的方式进行大规模重新定位。这代表了稳态可塑性的一种形式，其中神经元通过改变AIS的大小和/或位置来调节自己的兴奋性。虽然AIS可塑性对于含有AIS的神经元的正常功能很重要，对AIS可塑性的细胞和分子机制了解甚少。这里,我们使用3D结构化照明显微镜（3D-SIM）分析了AIS可塑性过程中AIS肌动蛋白细胞骨架的变化。我们表明，可塑性诱导后3小时，纵向肌动蛋白纤维的数量短暂增加。我们进一步证明肌动蛋白聚合，尤其是双胍介导的肌动蛋白聚合，是AIS可塑性和纵向肌动蛋白纤维形成所必需的。从formin家族的蛋白质中，Daam1定位于纵向肌动蛋白纤维的末端。这些结果表明，适当的AIS可塑性需要肌动蛋白细胞骨架的主动重组。
