Growth cone macropinocytosis of neurotrophin receptor and neuritogenesis are regulated by neuron navigator 1.
Growth cone macropinocytosis of neurotrophin receptor and neuritogenesis are regulated by neuron navigator 1.
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DOI：
10.1091/mbc.e21-12-0623
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发表时间：
2022-06-01
影响因子：
3.3
通讯作者：
Halpain, Shelley
中科院分区：
文献类型：
--
作者：
Powers, Regina M.;Daza, Ray;Koehler, Alanna E.;Courchet, Julien;Calabrese, Barbara;Hevner, Robert F.;Halpain, Shelley
Neuron navigator 1（Nav 1）是一种在大脑发育过程中表达的细胞因子相关蛋白，是正确的轴突发生所必需的，但其潜在机制尚不清楚。在这里，我们表明，Nav 1是存在于延长轴突束在小鼠脑胚胎发生。我们发现，在培养的神经元中Nav 1的耗竭破坏了生长锥形态和神经营养素刺激的轴突发生。除了调节F-肌动蛋白和微管特性，Nav 1还促进生长锥中富含肌动蛋白的膜皱褶，并促进这些膜皱褶处的巨胞饮作用，包括神经营养因子脑源性神经营养因子（BDNF）的TrkB受体的内化。生长锥巨胞饮作用对于下游信号传导、神经突靶向和膜再循环是重要的，暗示Nav 1参与这些过程中的一个或多个。Nav 1的消耗还通过Rho GT3信号通路中的信号传导的破坏诱导瞬时膜起泡，支持Nav 1在细胞外周基于肌动蛋白的动态膜调节中的新作用。这些数据表明，Nav 1在微管，肌动蛋白和质膜的界面上工作，以组织细胞周边，并促进对生长和引导线索的摄取，以促进发育期间的神经形态发生。
Neuron navigator 1 (Nav1) is a cytoskeleton-associated protein expressed during brain development that is necessary for proper neuritogenesis, but the underlying mechanisms are poorly understood. Here we show that Nav1 is present in elongating axon tracts during mouse brain embryogenesis. We found that depletion of Nav1 in cultured neurons disrupts growth cone morphology and neurotrophin-stimulated neuritogenesis. In addition to regulating both F-actin and microtubule properties, Nav1 promotes actin-rich membrane ruffles in the growth cone and promotes macropinocytosis at those membrane ruffles, including internalization of the TrkB receptor for the neurotrophin brain-derived neurotropic factor (BDNF). Growth cone macropinocytosis is important for downstream signaling, neurite targeting, and membrane recycling, implicating Nav1 in one or more of these processes. Depletion of Nav1 also induces transient membrane blebbing via disruption of signaling in the Rho GTPase signaling pathway, supporting the novel role of Nav1 in dynamic actin-based membrane regulation at the cell periphery. These data demonstrate that Nav1 works at the interface of microtubules, actin, and plasma membrane to organize the cell periphery and promote uptake of growth and guidance cues to facilitate neural morphogenesis during development.
DOI：
10.1083/jcb.102.4.1510
发表时间：
1986-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bridgman PC;Kachar B;Reese TS
通讯作者：
Reese TS