Shikanai Mima, Nishimura Yoshiaki V, Sakurai Miwa, Nabeshima Yo-Ichi, Yuzaki Michisuke, Kawauchi Takeshi
Department of Physiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Division of Neuroscience, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 1-15-1 Fukumuro, Miyaginoku, Sendai, Miyagi 983-8536, Japan.
iScience. 2018 Sep 28;7:53-67. doi: 10.1016/j.isci.2018.08.014. Epub 2018 Aug 21.
Axon specification is morphologically reproducible in vitro, whereas dendrite formation differs in vitro and in vivo. Cortical neurons initially develop immature neurites, but in vivo these are eliminated concurrently with the formation of a leading process, the future dendrite. However, the molecular mechanisms underlying these neuronal maturation events remain unclear. Here we show that caveolin-1, a major component of caveolae that are never observed in neurons, regulates in vivo-specific steps of neuronal maturation. Caveolin-1 is predominantly expressed in immature cortical neurons and regulates clathrin-independent endocytosis. In vivo knockdown of caveolin-1 disturbs immature neurite pruning, leading process elongation, and subsequent neuronal migration. Importantly, N-cadherin and L1, which are required for immature neurite formation, undergo caveolin-1-mediated endocytosis to eliminate immature neurites. Collectively, our findings indicate that caveolin-1 regulates N-cadherin and L1 trafficking independent of caveolae, which contributes to spatiotemporally restricted cellular events; immature neurite pruning and leading process elongation during early neuronal maturation.
轴突特化在体外具有形态学上的可重复性，而树突形成在体外和体内存在差异。皮层神经元最初发育出不成熟的神经突，但在体内，这些神经突会随着主导突起（未来的树突）的形成而同时被消除。然而，这些神经元成熟事件背后的分子机制仍不清楚。在这里，我们表明小窝蛋白-1（一种在神经元中从未观察到的小窝的主要成分）调节神经元成熟的体内特定步骤。小窝蛋白-1主要在未成熟的皮层神经元中表达，并调节网格蛋白非依赖性内吞作用。在体内敲减小窝蛋白-1会干扰未成熟神经突的修剪、主导突起的延长以及随后的神经元迁移。重要的是，未成熟神经突形成所需的N-钙黏蛋白和L1会经历小窝蛋白-1介导的内吞作用以消除未成熟神经突。总的来说，我们的研究结果表明，小窝蛋白-1独立于小窝调节N-钙黏蛋白和L1的运输，这有助于时空受限的细胞事件；早期神经元成熟过程中未成熟神经突的修剪和主导突起的延长。
