PDF(Pubmed)
Abstract：
In neurons, the microtubule (MT) cytoskeleton forms the basis for long-distance protein transport from the cell body into and out of dendrites and axons. To maintain neuronal polarity, the axon initial segment (AIS) serves as a physical barrier, separating the axon from the somatodendritic compartment and acting as a filter for axonal cargo. Selective trafficking is further instructed by axonal enrichment of MT post-translational modifications, which affect MT dynamics and the activity of motor proteins. Here, we compared two knockout mouse lines lacking the respective enzymes for MT tyrosination and detyrosination, and found that both knockouts led to a shortening of the AIS. Neurons from both lines also showed an increased immobile fraction of endolysosomes present in the axon, whereas mobile organelles displayed shortened run distances in the retrograde direction. Overall, our results highlight the importance of maintaining the balance of tyrosinated and detyrosinated MTs for proper AIS length and axonal transport processes.
摘要：
在神经元中，微管（MT）细胞骨架构成了蛋白质从细胞体进出树突和轴突的长距离运输的基础。为了维持神经元的极性,轴突初始段(AIS)充当物理屏障，将轴突与树枝状区室分离，并充当轴突货物的过滤器。通过MT翻译后修饰的轴突富集进一步指示选择性贩运，影响MT动力学和运动蛋白的活性。这里,我们比较了缺乏MT酪氨酸化和去酪氨酸化各自酶的两个敲除小鼠系，发现两个敲除都导致AIS缩短。来自两系的神经元也显示轴突中存在的内溶酶体的固定分数增加，而移动细胞器在逆行方向显示缩短的运行距离。总的来说,我们的研究结果突出表明,对于适当的AIS长度和轴突运输过程,保持酪氨酸化和去酪氨酸化的MTs平衡的重要性.
