A two-step actin polymerization mechanism drives dendrite branching.
A two-step actin polymerization mechanism drives dendrite branching.
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DOI：
10.1186/s13064-021-00154-0
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发表时间：
2021-07-19
影响因子：
3.6
通讯作者：
Shen K
中科院分区：
文献类型：
--
作者：
Shi R;Kramer DA;Chen B;Shen K
在神经系统发育过程中，树枝状突起的形态发生在建立神经元的连接性和感受野方面发挥着至关重要的作用。为了产生分支树突的不同形态，神经元使用外部信号和细胞表面受体来协调细胞内的细胞骨架组织;然而，这种信号传导如何形成分支树突的分子机制尚未完全理解。我们对C.在肌动蛋白调节蛋白的几种突变体中，例如WAVE调节复合物（WRC）和ENA-34（使能/血管舒张刺激磷蛋白（Ena/VASP）的同源物）中发现了秀丽隐杆线虫。我们检测了WRC和GFP-34之间的直接相互作用，并使用表达GFP-34的转基因蠕虫分析了GFP-34在体内的定位。我们确定了一个刻板的序列的形态学事件在树突生长过程中的PVD神经元在C。优雅具体而言，局部宽度增加（“south”）引起丝状伪足，以促进“快速生长和暂停”的生长模式。在unc-34突变体中，丝状伪足不能形成，但丝状伪足完整。在WRC突变体中，由于缺乏肿胀和丝状伪足形成，树突生长基本上不存在。我们还发现，α-34可以直接与WRC结合。通过删除β-34 EVH 1结构域来破坏这种结合，可以防止β-34定位于表皮和树突尖端，导致发育不良的树突乔木和减少的丝状伪足生长。我们建议，监管机构的分支和线性F-肌动蛋白合作，建立树突状分支。通过结合我们的工作与现有文献，我们提出树突导向受体DMA-1招聘的WRC，聚合分支的F-肌动蛋白，以产生“south”的母亲树突。然后，WRC招募肌动蛋白延伸因子<$3 -34/Ena/VASP，在肌动蛋白结合蛋白<$3 -115/abLIM的帮助下，从肿胀处开始生长新的树突状分支。现有枝晶的延伸也通过枝晶尖端的肿胀形成以及随后的UNC-34介导的生长来进行。在树突起始和延伸之后，通过引导受体的分支的稳定进一步招募WRC，导致迭代过程以构建复杂的树突乔木。在线版本包含补充材料，可通过10.1186/s13064-021-00154-0获得。
Dendrite morphogenesis plays an essential role in establishing the connectivity and receptive fields of neurons during the development of the nervous system. To generate the diverse morphologies of branched dendrites, neurons use external cues and cell surface receptors to coordinate intracellular cytoskeletal organization; however, the molecular mechanisms of how this signaling forms branched dendrites are not fully understood. We performed in vivo time-lapse imaging of the PVD neuron in C. elegans in several mutants of actin regulatory proteins, such as the WAVE Regulatory Complex (WRC) and UNC-34 (homolog of Enabled/Vasodilator-stimulated phosphoprotein (Ena/VASP)). We examined the direct interaction between the WRC and UNC-34 and analyzed the localization of UNC-34 in vivo using transgenic worms expressing UNC-34 fused to GFP. We identify a stereotyped sequence of morphological events during dendrite outgrowth in the PVD neuron in C. elegans. Specifically, local increases in width (“swellings”) give rise to filopodia to facilitate a “rapid growth and pause” mode of growth. In unc-34 mutants, filopodia fail to form but swellings are intact. In WRC mutants, dendrite growth is largely absent, resulting from a lack of both swelling and filopodia formation. We also found that UNC-34 can directly bind to the WRC. Disrupting this binding by deleting the UNC-34 EVH1 domain prevented UNC-34 from localizing to swellings and dendrite tips, resulting in a stunted dendritic arbor and reduced filopodia outgrowth. We propose that regulators of branched and linear F-actin cooperate to establish dendritic branches. By combining our work with existing literature, we propose that the dendrite guidance receptor DMA-1 recruits the WRC, which polymerizes branched F-actin to generate “swellings” on a mother dendrite. Then, WRC recruits the actin elongation factor UNC-34/Ena/VASP to initiate growth of a new dendritic branch from the swelling, with the help of the actin-binding protein UNC-115/abLIM. Extension of existing dendrites also proceeds via swelling formation at the dendrite tip followed by UNC-34-mediated outgrowth. Following dendrite initiation and extension, the stabilization of branches by guidance receptors further recruits WRC, resulting in an iterative process to build a complex dendritic arbor. The online version contains supplementary material available at 10.1186/s13064-021-00154-0.
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肌动蛋白调节波复合物的结构和控制。
影响因子：
64.8
作者：
Chen, Zhucheng;Borek, Dominika;Padrick, Shae B.;Gomez, Timothy S.;Metlagel, Zoltan;Ismail, Ayman M.;Umetani, Junko;Billadeau, Daniel D.;Otwinowski, Zbyszek;Rosen, Michael K.
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