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mRNA 定位和蛋白质合成位点如何影响树突蛋白的分布和动态。

How mRNA Localization and Protein Synthesis Sites Influence Dendritic Protein Distribution and Dynamics.

机构信息

Max Planck Institute for Brain Research, Theory of Neural Dynamics Group, Frankfurt am Main, Germany; Emory University School of Medicine, Atlanta, GA, USA.

Max Planck Institute for Brain Research, Theory of Neural Dynamics Group, Frankfurt am Main, Germany.

出版信息

Neuron. 2019 Sep 25;103(6):1109-1122.e7. doi: 10.1016/j.neuron.2019.06.022. Epub 2019 Jul 23.

Abstract

Proteins drive the function of neuronal synapses. The synapses are distributed throughout the dendritic arbor, often hundreds of micrometers away from the soma. It is still unclear how somatic and dendritic sources of proteins shape protein distribution and respectively contribute to local protein changes during synaptic plasticity. Here, we present a unique computational framework describing for a given protein species the dendritic distribution of the mRNA and the corresponding protein in a dendrite. Using CaMKIIα as a test case, our model reveals the key role active transport plays in the maintenance of dendritic mRNA and protein levels and predicts the short and long timescales of protein dynamics. Our model reveals the fundamental role of mRNA localization and dendritic mRNA translation in synaptic maintenance and plasticity in distal compartments. We developed a web application for neuroscientists to explore the dynamics of the mRNA or protein of interest.

摘要

蛋白质驱动神经元突触的功能。突触分布在树突的整个分支上,通常距离胞体数百微米。目前尚不清楚蛋白质的体部和树突来源如何塑造蛋白质的分布,并分别在突触可塑性过程中导致局部蛋白质变化。在这里,我们提出了一个独特的计算框架,用于描述给定蛋白质物种的 mRNA 和相应蛋白质在树突中的树突分布。使用 CaMKIIα 作为测试案例,我们的模型揭示了主动运输在维持树突 mRNA 和蛋白质水平方面的关键作用,并预测了蛋白质动力学的短时间和长时间尺度。我们的模型揭示了 mRNA 定位和树突 mRNA 翻译在远端隔室的突触维持和可塑性中的基本作用。我们为神经科学家开发了一个网络应用程序,以探索感兴趣的 mRNA 或蛋白质的动力学。

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