Dendritic arbor development is a complex, highly regulated process. Post-transcriptional regulation mediated by RNA-binding proteins plays an important role in neuronal dendrite morphogenesis by delivering on-site, on-demand protein synthesis. Here, we show how the Drosophila fragile X mental retardation protein (FMRP), a conserved RNA-binding protein, limits dendrite branching to ensure proper neuronal function during larval sensory neuron development. FMRP knockdown causes increased dendritic terminal branch growth and a resulting overelaboration defect due, in part, to altered microtubule stability and dynamics. FMRP also controls dendrite outgrowth by regulating the Drosophila profilin homolog chickadee (chic). FMRP colocalizes with chic mRNA in dendritic granules and regulates its dendritic localization and protein expression. Whereas RNA-binding domains KH1 and KH2 are both crucial for FMRP-mediated dendritic regulation, KH2 specifically is required for FMRP granule formation and chic mRNA association, suggesting a link between dendritic FMRP granules and FMRP function in dendrite elaboration. Our studies implicate FMRP-mediated modulation of both the neuronal microtubule and actin cytoskeletons in multidendritic neuronal architecture, and provide molecular insight into FMRP granule formation and its relevance to FMRP function in dendritic patterning.

中文翻译：

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果蝇脆性 X 智力迟钝蛋白调节神经元细胞骨架以限制树突树枝状化。

树突状乔木的发育是一个复杂的、高度调控的过程。由 RNA 结合蛋白介导的转录后调控通过提供现场按需蛋白质合成，在神经元树突形态发生中发挥重要作用。在这里，我们展示了果蝇脆性 X 智力迟钝蛋白 (FMRP)，一种保守的 RNA 结合蛋白，如何限制树突分支以确保幼虫感觉神经元发育过程中的正常神经元功能。FMRP 敲低导致树突末端分支生长增加，并导致过度加工缺陷，部分原因是微管稳定性和动力学改变。FMRP 还通过调节果蝇 profilin 同源山雀 (chic) 来控制树突的生长。FMRP 与树突颗粒中的别致 mRNA 共定位并调节其树突定位和蛋白质表达。尽管 RNA 结合结构域 KH1 和 KH2 对于 FMRP 介导的树突调节至关重要，但 KH2 是 FMRP 颗粒形成和别致 mRNA 结合所必需的，这表明树突 FMRP 颗粒与 FMRP 在树突加工中的功能之间存在联系。我们的研究表明 FMRP 介导的多树突神经元结构中神经元微管和肌动蛋白细胞骨架的调节，并提供了对 FMRP 颗粒形成及其与树突模式中 FMRP 功能的相关性的分子洞察。