研究人员使用空间蛋白质组学来阐明人类诱导多能干细胞衍生的神经干细胞（NSC）和神经元中心体的蛋白质相互作用网络。中心体相关蛋白主要是细胞类型特异性的，蛋白质中枢参与RNA动力学。对神经发育疾病队列的分析发现，在脑室周围异位（PH）患者中，NSC中心体蛋白的变异明显过多。表达PH相关突变的前mRNA加工因子6（PRPF6）再现了发育中的小鼠大脑中的脑室周围错位，突出了具有中心体位置的微管相关激酶转录本的错误拼接，这是表型所必需的。
总的来说，细胞类型特异性中心体相互作用组解释了普遍存在的蛋白质中的遗传变异如何传达大脑特异性表型。
据介绍，中心体为细胞骨架提供细胞内锚定，调节细胞分裂、细胞迁移和纤毛的形成。
附：英文原文
Title: Spatial centrosome proteome of human neural cells uncovers disease-relevant heterogeneity
Author: Adam C. O’Neill, Fatma Uzbas, Giulia Antognolli, Florencia Merino, Kalina Draganova, Alex Jck, Sirui Zhang, Giorgia Pedini, Julia P. Schessner, Kimberly Cramer, Aloys Schepers, Fabian Metzger, Miriam Esgleas, Pawel Smialowski, Renzo Guerrini, Sven Falk, Regina Feederle, Saskia Freytag, Zefeng Wang, Melanie Bahlo, Ralf Jungmann, Claudia Bagni, Georg H. H. Borner, Stephen P. Robertson, Stefanie M. Hauck, Magdalena Gtz
Issue&Volume: 2022-06-17
Abstract: The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, cell migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at the centrosome of human induced pluripotent stem cell–derived neural stem cells (NSCs) and neurons. Centrosome-associated proteins were largely cell type–specific, with protein hubs involved in RNA dynamics. Analysis of neurodevelopmental disease cohorts identified a significant overrepresentation of NSC centrosome proteins with variants in patients with periventricular heterotopia (PH). Expressing the PH-associated mutant pre-mRNA-processing factor 6 (PRPF6) reproduced the periventricular misplacement in the developing mouse brain, highlighting missplicing of transcripts of a microtubule-associated kinase with centrosomal location as essential for the phenotype. Collectively, cell type–specific centrosome interactomes explain how genetic variants in ubiquitous proteins may convey brain-specific phenotypes.
DOI: abf9088
Source: https://www.science.org/doi/10.1126/science.abf9088