Fragile X granules are a family of axonal ribonucleoprotein particles with circuit-dependent protein composition and mRNA cargos.
Fragile X granules are a family of axonal ribonucleoprotein particles with circuit-dependent protein composition and mRNA cargos.
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DOI：
10.1002/cne.24321
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发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Akins MR
中科院分区：
文献类型：
--
作者：
Chyung E;LeBlanc HF;Fallon JR;Akins MR
局部轴突蛋白质合成在神经回路的形成和功能中起着至关重要的作用。要了解这种机制在特定回路中的作用，需要确定形成轴突翻译底物的核糖核蛋白颗粒（RNP）的蛋白质组成和mRNA货物。FXG（脆性X颗粒）是存在于完整脑中成熟轴突的定型子集中的轴突RNP，其含有一种或多种脆性X相关（FXR）蛋白（FMRP、FXR 2 P和FXR 1 P）以及沿着mRNA和核糖体。在这里，我们进行了一个系统的调查FXR蛋白组成和FXGs在大脑中的mRNA协会。我们已经确定了四种FXG类型，可以根据其FXR蛋白互补进行分类。所有FXG都含有FXR 2 P，FMRP和/或FXR 1 P存在于电路选择性子集中。个别神经元细胞类型主要表达单一FXG类型，其中含FMRP的FXG在前脑神经元中最普遍。所有FXG类型都与核糖体和mRNA相关，但特定的mRNA货物是FXG类型、脑区域和神经元类别的功能。β-连环蛋白及其调节因子APC的转录物与前脑FXG的子集相关。此外，这两种转录本可以在单个FXGs内共定位，这表明功能相关蛋白的轴突翻译可以以高时空分辨率协调调节。具有不同mRNA货物（如FXG）的特定RNP类型的细胞类型依赖性表达呈现出以回路依赖性方式调节局部翻译及其输出的潜在机制。
Local axonal protein synthesis plays a crucial role in the formation and function of neuronal circuits. Understanding the role of this mechanism in specific circuits requires identifying the protein composition and mRNA cargos of the ribonucleoprotein particles (RNPs) that form the substrate for axonal translation. FXGs (Fragile X granules) are axonal RNPs present in a stereotyped subset of mature axons in the intact brain that contain one or more of the Fragile X related (FXR) proteins (FMRP, FXR2P, and FXR1P) along with mRNA and ribosomes. Here we performed a systematic survey of the FXR protein composition and mRNA association of FXGs in the brain. We have identified four FXG types that can be categorized based on their FXR protein complement. All FXGs contain FXR2P, with FMRP and/or FXR1P present in circuit-selective subsets. Individual neuronal cell types predominantly express a single FXG type, with FMRP-containing FXGs the most prevalent in forebrain neurons. All FXG types associate with ribosomes and mRNA, but the specific mRNA cargos are a function of FXG type, brain region and neuron class. Transcripts for β-catenin and its regulator APC associate with a subset of forebrain FXGs. Moreover, both these transcripts can colocalize within individual FXGs, suggesting that the axonal translation of functionally related proteins may be coordinately regulated with high spatiotemporal resolution. Cell type-dependent expression of specific RNP types with distinct mRNA cargos, such as FXGs, presents a potential mechanism for regulating local translation and its output in a circuit-dependent manner.
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