Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development.
Myosin X Interaction with KIF13B, a Crucial Pathway for Netrin-1-Induced Axonal Development.
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DOI：
10.1523/jneurosci.0929-20.2020
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发表时间：
2020-11-25
期刊：
影响因子：
--
通讯作者：
Xiong WC
中科院分区：
文献类型：
--
作者：
Yu HL;Peng Y;Zhao Y;Lan YS;Wang B;Zhao L;Sun D;Pan JX;Dong ZQ;Mei L;Ding YQ;Zhu XJ;Xiong WC
肌球蛋白X(Myo X)将货物运输到丝状伪足的顶端，用于细胞黏附、迁移和神经元轴突的引导。在结直肠癌中缺失的基因(DCC)是一种Myo X基因，在Netrin-1调控的轴突通路中起着至关重要的作用。Myo X在体内轴突发育中的作用及其机制仍不清楚。在此，我们提供了Myo X在Netrin-1-DCC调节的小鼠新皮质发育中轴突发育中的作用的证据。胚胎小鼠大脑皮层神经元Myo X基因敲除(KO)或敲除(KD)会损害轴突的起始和对侧分支/靶向。在Netrin-1-KO或DCC-KD皮质神经元中也检测到类似的轴突缺失。对Myo X结合蛋白的进一步蛋白质组学分析确定了KIF13B(一种激动素家族运动蛋白)。Myo X与KIF13B的相互作用是由Netrin-1诱导的。Netrin-1以KIF13B依赖的方式促进Myo X向轴突的顺行转运。KIF13B-KD皮层神经元表现出类似的轴突缺陷。综上所述，这些结果揭示了Myo X-KIF13B是Netrin-1促进的轴突起始和分支/靶向的关键途径。意义声明Netrin-1增加了肌球蛋白X(Myo X)与KIF13B的相互作用，从而促进了Myo X的轴突递送以及发育中的大脑神经元的轴突起始和对侧分支，揭示了Netrin-1调节轴突发育的未知功能和机制。
Myosin X (Myo X) transports cargos to the tips of filopodia for cell adhesion, migration, and neuronal axon guidance. Deleted in Colorectal Cancer (DCC) is one of the Myo X cargos that is essential for Netrin-1-regulated axon pathfinding. The function of Myo X in axon development in vivo and the underlying mechanisms remain elusive. Here, we provide evidence for the role of Myo X in Netrin-1-DCC-regulated axon development in developing mouse neocortex. The knockout (KO) or knockdown (KD) of Myo X in cortical neurons of embryonic mouse brain impairs axon initiation and contralateral branching/targeting. Similar axon deficits are detected in Netrin-1-KO or DCC-KD cortical neurons. Further proteomic analysis of Myo X binding proteins identifies KIF13B (a kinesin family motor protein). The Myo X interaction with KIF13B is induced by Netrin-1. Netrin-1 promotes anterograde transportation of Myo X into axons in a KIF13B-dependent manner. KIF13B-KD cortical neurons exhibit similar axon deficits. Together, these results reveal Myo X-KIF13B as a critical pathway for Netrin-1-promoted axon initiation and branching/targeting. SIGNIFICANCE STATEMENT Netrin-1 increases Myosin X (Myo X) interaction with KIF13B, and thus promotes axonal delivery of Myo X and axon initiation and contralateral branching in developing cerebral neurons, revealing unrecognized functions and mechanisms underlying Netrin-1 regulation of axon development.
影响因子：
2.5
作者：
Hwang, Yoo-Seok;Luo, Ting;Xu, Yanhua;Sargent, Thomas D.
通讯作者：
Sargent, Thomas D.