NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity.
NgCAM and VAMP2 reveal that direct delivery and dendritic degradation maintain axonal polarity.
复制标题
DOI：
10.1091/mbc.e21-08-0425
复制
发表时间：
2022-01-01
影响因子：
3.3
通讯作者：
Bentley M
中科院分区：
文献类型：
--
作者：
Nabb AT;Bentley M
神经元是具有极端规模和区室化的极化细胞。为了发挥其在电化学信号传导中的作用，轴突必须维持膜蛋白的特定补充。尽管受到相当多的关注，但轴突膜蛋白的运输途径尚不清楚。已经提出了两种途径：直接递送和转胞吞作用。先前的研究得出了关于哪些介导轴突膜蛋白到达目的地的相互矛盾的结论，部分原因是他们评估了长期分布变化而不是囊泡运输。我们开发了一种新策略来选择性标记不同运输途径中的囊泡，并确定了两种典型轴突膜蛋白、神经元-胶质细胞粘附分子和囊泡相关膜蛋白-2的运输。运输囊泡详细定量分析的结果与之前的研究有很大不同，发现轴突膜蛋白绝大多数是直接运输的。转胞吞作用在这些蛋白质的轴突递送中仅发挥次要作用。此外，我们还发现了一种新的途径，通过该途径，到达树突质膜的任性轴突蛋白靶向溶酶体。这些结果重新定义了轴突蛋白如何实现极化分布，这是阐明潜在分子机制的关键要求。
Neurons are polarized cells of extreme scale and compartmentalization. To fulfill their role in electrochemical signaling, axons must maintain a specific complement of membrane proteins. Despite being the subject of considerable attention, the trafficking pathway of axonal membrane proteins is not well understood. Two pathways, direct delivery and transcytosis, have been proposed. Previous studies reached contradictory conclusions about which of these mediates delivery of axonal membrane proteins to their destination, in part because they evaluated long-term distribution changes and not vesicle transport. We developed a novel strategy to selectively label vesicles in different trafficking pathways and determined the trafficking of two canonical axonal membrane proteins, neuron–glia cell adhesion molecule and vesicle-associated membrane protein-2. Results from detailed quantitative analyses of transporting vesicles differed substantially from previous studies and found that axonal membrane proteins overwhelmingly undergo direct delivery. Transcytosis plays only a minor role in axonal delivery of these proteins. In addition, we identified a novel pathway by which wayward axonal proteins that reach the dendritic plasma membrane are targeted to lysosomes. These results redefine how axonal proteins achieve their polarized distribution, a crucial requirement for elucidating the underlying molecular mechanisms.