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火烈鸟 FMI-1 通过 F-肌动蛋白组装来控制树突的自回避。

Flamingo FMI-1 controls dendrite self-avoidance through F-actin assembly.

机构信息

Institute of Molecular Medicine and Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.

Institute of Molecular Medicine and Center of Precision Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan

出版信息

Development. 2020 Jul 31;147(14):dev179168. doi: 10.1242/dev.179168.

Abstract

Self-avoidance is a conserved mechanism that prevents crossover between sister dendrites from the same neuron, ensuring proper functioning of the neuronal circuits. Several adhesion molecules are known to be important for dendrite self-avoidance, but the underlying molecular mechanisms are incompletely defined. Here, we show that FMI-1/Flamingo, an atypical cadherin, is required autonomously for self-avoidance in the multidendritic PVD neuron of The mutant shows increased crossover between sister PVD dendrites. Our genetic analysis suggests that FMI-1 promotes transient F-actin assembly at the tips of contacting sister dendrites to facilitate their efficient retraction during self-avoidance events, probably by interacting with WSP-1/N-WASP. Mutations of , which encodes the planar cell polarity protein Vangl2 previously shown to inhibit F-actin assembly, suppress self-avoidance defects of the mutant. FMI-1 downregulates VANG-1 levels probably through forming protein complexes. Our study identifies molecular links between Flamingo and the F-actin cytoskeleton that facilitate efficient dendrite self-avoidance.

摘要

自我回避是一种保守的机制,可防止来自同一神经元的姐妹树突之间的交叉,从而确保神经元回路的正常功能。已知几种粘附分子对于树突自我回避很重要,但潜在的分子机制尚不完全明确。在这里,我们表明,FMI-1/Flamingo,一种非典型的钙粘蛋白,自主地需要用于多树突 PVD 神经元的自我回避,在 突变体中观察到姐妹 PVD 树突之间的交叉增加。我们的遗传分析表明,FMI-1 促进接触的姐妹树突末端的瞬态 F-肌动蛋白组装,以促进它们在自我回避事件期间的有效回缩,可能通过与 WSP-1/N-WASP 相互作用。先前显示抑制 F-肌动蛋白组装的平面细胞极性蛋白 Vangl2 的 编码基因突变可抑制 突变体的自我回避缺陷。FMI-1 可能通过形成蛋白复合物下调 VANG-1 水平。我们的研究确定了 Flamingo 与促进有效树突自我回避的 F-肌动蛋白细胞骨架之间的分子联系。

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