Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of Caenorhabditis elegans, synapses of motor neurons are stereotypically rewired through a process facilitated by dynamic microtubules (MTs). Through a genetic suppressor screen on mutant animals that fail to rewire synapses, and in combination with live imaging and ultrastructural studies, we find that intermediate filaments (IFs) stabilize MTs to prevent synapse rewiring. Genetic ablation of IFs or pharmacological disruption of IF networks restores MT growth and rescues synapse rewiring defects in the mutant animals, indicating that IF accumulation directly alters MT stability. Our work sheds light on the impact of IFs on MT dynamics and axonal transport, which is relevant to the mechanistic understanding of several human motor neuron diseases characterized by IF accumulation in axonal swellings.

神经回路利用协调的细胞机制来形成和消除突触连接，其中神经元的细胞骨架起着重要的作用。秀丽隐杆线虫幼虫发育期间运动神经元的突触通过动态微管（MT）促进的过程被定型地重新布线。通过对不能重新连接突触的突变动物进行基因抑制器筛选，并与实时成像和超微结构研究相结合，我们发现中间丝（IFs）使MT稳定化以防止突触重新接线。IFs的遗传消融或IF网络的药理学破坏可恢复MT的生长并挽救突变动物的突触重新接线缺陷，这表明IF的积累直接改变了MT的稳定性。我们的工作揭示了IF对MT动力学和轴突运输的影响，这与对以IF在轴突肿胀中积累为特征的几种人类运动神经元疾病的机理了解有关。