Seno Takeshi, Ikeno Tatsuki, Mennya Kousuke, Kurishita Masayuki, Sakae Narumi, Sato Makoto, Takada Hiroki, Konishi Yoshiyuki
Department of Human and Artificial Intelligence Systems, University of Fukui, Fukui 910-8507, Japan.
Life Science Innovation Center, University of Fukui, Fukui 910-8507, Japan Research Center for Child Mental Development, University of Fukui, Fukui 910-1193, Japan Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan United Graduate School of Child Development, Osaka University, Kanazawa University-Hamamatsu University School of Medicine, Chiba University and University of Fukui, Osaka University, Osaka 565-0871, Japan.
J Cell Sci. 2016 Sep 15;129(18):3499-510. doi: 10.1242/jcs.183806. Epub 2016 Aug 5.
The ability of neurons to generate multiple arbor terminals from a single axon is crucial for establishing proper neuronal wiring. Although growth and retraction of arbor terminals are differentially regulated within the axon, the mechanisms by which neurons locally control their structure remain largely unknown. In the present study, we found that the kinesin-1 (Kif5 proteins) head domain (K5H) preferentially marks a subset of arbor terminals. Time-lapse imaging clarified that these arbor terminals were more stable than others, because of a low retraction rate. Local inhibition of kinesin-1 in the arbor terminal by chromophore-assisted light inactivation (CALI) enhanced the retraction rate. The microtubule turnover was locally regulated depending on the length from the branching point to the terminal end, but did not directly correlate with the presence of K5H. By contrast, F-actin signal values in arbor terminals correlated spatiotemporally with K5H, and inhibition of actin turnover prevented retraction. Results from the present study reveal a new system mediated by kinesin-1 sorting in axons that differentially controls stability of arbor terminals.
神经元从单个轴突产生多个树突末梢的能力对于建立适当的神经元连接至关重要。尽管树突末梢的生长和回缩在轴突内受到不同的调节，但神经元局部控制其结构的机制在很大程度上仍不清楚。在本研究中，我们发现驱动蛋白-1（Kif5蛋白）头部结构域（K5H）优先标记树突末梢的一个子集。延时成像表明，这些树突末梢比其他树突末梢更稳定，因为回缩率较低。通过发色团辅助光灭活（CALI）在树突末梢局部抑制驱动蛋白-1可提高回缩率。微管周转率根据从分支点到末端的长度进行局部调节，但与K5H的存在没有直接关联。相比之下，树突末梢中的F-肌动蛋白信号值在时空上与K5H相关，并且抑制肌动蛋白周转可防止回缩。本研究结果揭示了一种由轴突中驱动蛋白-1分选介导的新系统，该系统可差异控制树突末梢的稳定性。
