PDF(Pubmed)
Abstract：
The axon initial segment (AIS) is a specialized neuronal compartment required for action potential generation and neuronal polarity. However, understanding the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, using immuno-proximity biotinylation we further define the AIS proteome and its dynamic changes during neuronal maturation. Among the many AIS proteins identified, we show that SCRIB is highly enriched in the AIS both in vitro and in vivo, and exhibits a periodic architecture like the axonal spectrin-based cytoskeleton. We find that ankyrinG interacts with and recruits SCRIB to the AIS. However, loss of SCRIB has no effect on ankyrinG. This powerful and flexible approach further defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function.
摘要：
轴突初始节段(AIS)是动作电位产生和神经元极性所需的专门神经元区室。然而,理解调节AIS结构和功能的机制受到对其分子组成的不完全了解的阻碍。这里,使用免疫邻近生物素化，我们进一步定义了AIS蛋白质组及其在神经元成熟过程中的动态变化。在鉴定出的许多AIS蛋白中,我们表明SCRIB在体外和体内都高度富集在AIS中，并表现出周期性结构，如基于轴突光谱的细胞骨架。我们发现，ankyrinG与SCRIB相互作用，并将SCRIB招募到AIS。然而,SCRIB的损失对AnkyrinG没有影响。这种强大而灵活的方法进一步定义了AIS蛋白质组，并提供了丰富的资源来阐明调节AIS结构和功能的机制。
