Studies on the role of Pur α in BC1 RNA transport in neuronal dendrites

Pur α在神经元树突BC1 RNA转运中的作用研究

• 批准号: 13680853
• 负责人: ANZAI Kaijiro
• 金额: $ 1.86万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680853/
• 关键词: Brain; BC1 RNA; Pur α; RNA-transport; dendrite; RNA-binding protein; 神経細胞; mRNA輸送; 小胞輸送; Staufen; MyosinVa; FMRP; Kinesin5A; BC1 RNA; ポリソーム; タンパク合成; 分子モーター; 可塑性

Pur alpha, which is involved in diverse aspects of cellular functions, is strongly expressed in neuronal cytoplasm. Previously, we have reported that this protein controls BC1 RNA expression and its subsequent distribution within dendrites, and that pur alpha is associated with polyribosomes. Here, we report that, following treatment with EDTA, pur alpha was released from polyribosomes in mRNA/ protein complexes (mRNPs), which also contained mStaufen, Fragile X Mental Retardation Protein (FMRP), myosin Va and other proteins with unknown functions. As the coimmunoprecipitation of these proteins by an anti-pur alpha antibody was abolished by Rnase treatment, pur alpha may assist mRNP assembly in an RNA-dependent manner, and be involved in targeting mRNPs to polyribosomes in cooperation with other RNA-binding proteins. The immunoprecipitation of mStaufen- and FMRP-containing mRNPs provided additional evidence that the anti-pur alpha detected structurally or functionally related mRNA subsets which are distributed in the somatodendritic compartment. Furthermore, mRNPs appear to reside on rough endoplasmic reticulum (rER) equipped with a kinesin motor. Based on our present findings, we propose that this rER structure may form the molecular machinery that mediates and regulates multi-step transport of polyribosomes along microtubules and actin filaments, as well as localized translation in the somatodendritic compartment.More recently, studies on protein components of the mRNPs revealed that number of proteins implicated in metabolism of mRNAs or mRNA transport and translation were included. Moreover, several dendritic mRNAs were also associated with these complexes. It would be intriguing to further study the biological roles of pur alpha protein, together with other proteins, played in the process of mRNA transport in the neuronal dendrites.

Pur α 参与细胞功能的各个方面，在神经元细胞质中强烈表达。之前，我们报道过该蛋白控制 BC1 RNA 表达及其随后在树突内的分布，并且 pur alpha 与多核糖体相关。在此，我们报道，经过 EDTA 处理后，pur α 从 mRNA/蛋白质复合物 (mRNP) 中的多核糖体中释放出来，其中还含有 mStaufen、脆性 X 智力迟钝蛋白 (FMRP)、肌球蛋白 Va 和其他功能未知的蛋白质。由于 Rnase 处理消除了抗 pur α 抗体对这些蛋白质的共免疫沉淀，pur α 可能以 RNA 依赖性方式协助 mRNP 组装，并参与与其他 RNA 结合蛋白合作将 mRNP 靶向多核糖体。含有 mStaufen 和 FMRP 的 mRNP 的免疫沉淀提供了额外的证据，表明抗 pur α 检测到分布在体细胞树突区室中的结构或功能相关的 mRNA 子集。此外，mRNP 似乎驻留在配备有驱动蛋白马达的粗面内质网 (rER) 上。基于我们目前的发现，我们提出这种 rER 结构可能形成分子机制，介导和调节多核糖体沿着微管和肌动蛋白丝的多步运输，以及体细胞树突区室中的局部翻译。最近，对蛋白质成分的研究mRNP 的分析显示，其中包括与 mRNA 代谢或 mRNA 运输和翻译有关的蛋白质数量。此外，一些树突状 mRNA 也与这些复合物相关。进一步研究 pur α 蛋白以及其他蛋白质在神经元树突 mRNA 运输过程中所发挥的生物学作用将是很有趣的。