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黏附性 L1CAM-Robo 信号调节生长锥 F-肌动蛋白动力学,促进线虫的轴突-树突聚集。

Adhesive L1CAM-Robo Signaling Aligns Growth Cone F-Actin Dynamics to Promote Axon-Dendrite Fasciculation in C. elegans.

机构信息

Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.

Institute of Molecular Medicine, College of Medicine, National Taiwan University, No.7 Chung-Shan South Road, Taipei 10002, Taiwan.

出版信息

Dev Cell. 2019 Jan 28;48(2):215-228.e5. doi: 10.1016/j.devcel.2018.10.028. Epub 2018 Dec 13.

Abstract

Neurite fasciculation through contact-dependent signaling is important for the wiring and function of the neuronal circuits. Here, we describe a type of axon-dendrite fasciculation in C. elegans, where proximal dendrites of the nociceptor PVD adhere to the axon of the ALA interneuron. This axon-dendrite fasciculation is mediated by a previously uncharacterized adhesive signaling by the ALA membrane signal SAX-7/L1CAM and the PVD receptor SAX-3/Robo but independent of Slit. L1CAM physically interacts with Robo and instructs dendrite adhesion in a Robo-dependent manner. Fasciculation mediated by L1CAM-Robo signaling aligns F-actin dynamics in the dendrite growth cone and facilitates dynamic growth cone behaviors for efficient dendrite guidance. Disruption of PVD dendrite fasciculation impairs nociceptive mechanosensation and rhythmicity in body curvature, suggesting that dendrite fasciculation governs the functions of mechanosensory circuits. Our work elucidates the molecular mechanisms by which adhesive axon-dendrite signaling shapes the construction and function of sensory neuronal circuits.

摘要

通过接触依赖性信号传递进行神经突聚集对于神经元回路的布线和功能很重要。在这里,我们描述了秀丽隐杆线虫中一种轴突-树突聚集的类型,其中伤害感受器 PVD 的近端树突与 ALA 中间神经元的轴突黏附。这种轴突-树突聚集是由以前未被表征的 ALA 膜信号 SAX-7/L1CAM 和 PVD 受体 SAX-3/Robo 通过粘着信号传递介导的,但与 Slit 无关。L1CAM 与 Robo 物理相互作用,并以 Robo 依赖性方式指导树突黏附。由 L1CAM-Robo 信号介导的聚集将 F-肌动蛋白动力学在树突生长锥中对齐,并促进生长锥行为的动态变化,从而有效地指导树突。破坏 PVD 树突聚集会损害机械感觉的机械感觉和身体曲率的节律性,表明树突聚集控制机械感觉回路的功能。我们的工作阐明了粘着性轴突-树突信号传递塑造感觉神经元回路的结构和功能的分子机制。

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