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

Adhesive L1CAM-Robo Signaling Aligns Growth Cone F-Actin Dynamics to Promote Axon-Dendrite Fasciculation in C-elegans
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DOI:
10.1016/j.devcel.2018.10.028
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发表时间:
2019-01-28
期刊:
影响因子:
11.8
通讯作者:
Pan, Chun-Liang
Pan, Chun-Liang
中科院分区:
生物学1区
文献类型:
--
作者:
Chen, Chun-Hao;Hsu, Hao-Wei;Pan, Chun-Liang

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通过接触依赖性信号传导的神经突成束对于神经元回路的布线和功能是重要的。在这里,我们描述了一种类型的轴突树突成束在C。elegans,其中伤害感受器PVD的近端树突粘附在ALA中间神经元的轴突上。这种轴突-树突成束是由以前未表征的粘附信号通过ALA膜信号SAX-7/L1 CAM和PVD受体SAX-3/Robo介导的,但独立于Slit。L1 CAM与Robo物理相互作用,并以依赖于Robo的方式指导树突粘附。由L1 CAM-Robo信号传导介导的成束作用使树突生长锥中的F-肌动蛋白动力学对齐,并促进动态生长锥行为以实现有效的树突引导。PVD树突束分裂的中断损害伤害性机械感觉和身体弯曲的节律性,表明树突束分裂支配机械感觉回路的功能。我们的工作阐明了粘附性轴突树突信号塑造感觉神经元回路的结构和功能的分子机制。
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.