Translational and Posttranslational Dynamics in a Model Peptidergic System.
Translational and Posttranslational Dynamics in a Model Peptidergic System.
复制标题
DOI：
10.1016/j.mcpro.2023.100544
复制
发表时间：
2023-05
影响因子：
7
通讯作者：
Greenwood, Michael P
中科院分区：
文献类型：
--
作者：
Barez-Lopez, Soledad;Mecawi, Andre S;Bryan, Natasha;Pauza, Audrys G;Duque, Victor J;Gillard, Benjamin T;Murphy, David;Greenwood, Michael P
下丘脑大细胞神经元的胞体密集地排列在下丘脑视上核中，而它们的轴突投射到解剖学上离散的垂体后叶。我们已经利用这种独特的解剖结构，建立蛋白质组和磷酸化蛋白质组动力学的神经元细胞体和轴突终端响应生理刺激。我们已经发现，蛋白质组和磷酸化蛋白质组的神经元刺激反应是非常不同的体细胞和轴突神经元隔室之间，表明每个细胞域的差异适应的需要。特别是，在细胞体中的磷酸化蛋白质组的变化参与重组的细胞骨架和轴突终端的突触和分泌过程的调节。我们已经确定，激素前体，包括加压素和催产素的轴突终端磷酸化和过度磷酸化刺激后。通过转录组和蛋白质组数据的多组整合，我们确定了传入输入到这个核中的蛋白质的变化。不同神经元区室的蛋白质组学和磷酸蛋白质组学研究。轴突和躯体区室对生理刺激的反应是独特的。磷酸化改变重塑体细胞骨架和轴突突触前。激素前体对刺激的反应是过度磷酸化。在这项工作中，我们已经探讨了蛋白质组和磷酸化蛋白质组的体细胞神经元舱在视上核的下丘脑和它们的轴突投射在垂体基础和刺激条件下。通过与相应的视上核转录组的比较，我们带来了一个新的视角，转录组，蛋白质组和磷酸化蛋白质组动力学在这个独特的易于处理的模型神经元系统。
The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganization of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and are hyperphosphorylated following stimulation. By multiomic integration of transcriptome and proteomic data, we identify changes to proteins present in afferent inputs to this nucleus. Proteomic and phosphoproteomic investigation of distinct neuron compartments. Axonal and somatic compartments respond uniquely to physiological stimulation. Phosphorylation changes remodel the somatic cytoskeleton and the axonal presynapse. Hormone precursors become hyperphosphorylated in response to stimulation. In this work, we have explored the proteomes and phosphoproteomes of somatic neuronal compartments in the supraoptic nucleus of the hypothalamus and their axonal projections in the hypophysis under basal and stimulated conditions. Through comparisons with corresponding transcriptomes of the supraoptic nucleus, we bring a novel perspective to transcriptome, proteome, and phosphoproteome dynamics in this uniquely tractable model neuronal system.