KLC4 shapes axon arbors during development and mediates adult behavior.
KLC4 shapes axon arbors during development and mediates adult behavior.
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DOI：
10.7554/elife.74270
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发表时间：
2022-10-12
期刊：
影响因子：
7.7
通讯作者：
Halloran MC
中科院分区：
文献类型：
--
作者：
Haynes EM;Burnett KH;He J;Jean-Pierre MW;Jarzyna M;Eliceiri KW;Huisken J;Halloran MC
精细和极化的神经元形态的发展需要精确调节的运输细胞货物的马达蛋白，如驱动蛋白-1。驱动蛋白-1具有许多必须被递送到独特的神经元隔室的细胞货物。该马达选择性运输和递送货物以调节神经元形态发生的过程知之甚少，尽管货物结合驱动蛋白轻链（KLC）亚基有助于特异性。我们的工作涉及一个这样的亚基，KLC 4，作为一个重要的调节轴突分支和树枝化模式的感觉神经元在发展过程中。在klc 4突变斑马鱼中使用实时成像方法，我们表明KLC 4是新生轴突分支稳定，适当的微管（MT）动力学和内体运输所必需的。此外，KLC 4是必要的适当平铺外周轴突乔木：在kLC 4突变体，外周轴突表现出异常fasciculation，中央轴突的行为特征。这一结果表明，KLC 4模式轴突隔间，并帮助建立中央和外周轴突之间的分子差异。最后，我们发现klc 4突变的幼虫对触觉过敏，而成虫在一个新的水槽试验中表现出焦虑样行为，暗示klc 4是一个参与应激反应回路的新基因。
Development of elaborate and polarized neuronal morphology requires precisely regulated transport of cellular cargos by motor proteins such as kinesin-1. Kinesin-1 has numerous cellular cargos which must be delivered to unique neuronal compartments. The process by which this motor selectively transports and delivers cargo to regulate neuronal morphogenesis is poorly understood, although the cargo-binding kinesin light chain (KLC) subunits contribute to specificity. Our work implicates one such subunit, KLC4, as an essential regulator of axon branching and arborization pattern of sensory neurons during development. Using live imaging approaches in klc4 mutant zebrafish, we show that KLC4 is required for stabilization of nascent axon branches, proper microtubule (MT) dynamics, and endosomal transport. Furthermore, KLC4 is required for proper tiling of peripheral axon arbors: in klc4 mutants, peripheral axons showed abnormal fasciculation, a behavior characteristic of central axons. This result suggests that KLC4 patterns axonal compartments and helps establish molecular differences between central and peripheral axons. Finally, we find that klc4 mutant larva are hypersensitive to touch and adults show anxiety-like behavior in a novel tank test, implicating klc4 as a new gene involved in stress response circuits.
影响因子：
2.6
作者：
Bazvand F;Keramatipour M;Riazi-Esfahani H;Mahmoudi A
通讯作者：
Mahmoudi A