Experimental and computational framework for a dynamic protein atlas of human cell division

被引:83
作者
Cai, Yin [1 ,3 ]
Hossain, M. Julius [1 ]
Heriche, Jean-Karim [1 ]
Politi, Antonio Z. [1 ,4 ]
Walther, Nike [1 ]
Koch, Birgit [1 ,5 ]
Wachsmuth, Malte [1 ,6 ]
Nijmeijer, Bianca [1 ]
Kueblbeck, Moritz [1 ]
Martinic-Kavur, Marina [2 ,7 ]
Ladurner, Rene [2 ,8 ]
Alexander, Stephanie [1 ]
Peters, Jan-Michael [2 ]
Ellenberg, Jan [1 ]
机构
[1] EMBL, Heidelberg, Germany
[2] Res Inst Mol Pathol IMP, Vienna, Austria
[3] Roche Diagnost, Waiblingen, Germany
[4] Max Planck Inst Biophys Chem, Gottingen, Germany
[5] Max Planck Inst Med Res, Heidelberg, Germany
[6] Luxendo GmbH, Heidelberg, Germany
[7] Genos, Glycosci Res Lab, Zagreb, Croatia
[8] Stanford Sch Med, Stanford, CA USA
基金
欧盟第七框架计划; 欧洲研究理事会; 美国国家卫生研究院; 奥地利科学基金会; 欧盟地平线“2020”;
关键词
AURORA-B; GENOME; PHOSPHORYLATION; INTEGRATION; ANAPHASE; REVEALS; GENES;
D O I
10.1038/s41586-018-0518-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Essential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, the timing of interactions and changes in cellular structure are all crucial to ensure the correct assembly, function and regulation of protein complexes(1-4). Imaging of live cells can reveal protein distributions and dynamics but experimental and theoretical challenges have prevented the collection of quantitative data, which are necessary for the formulation of a model of mitosis that comprehensively integrates information and enables the analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries. Here we generate a canonical model of the morphological changes during the mitotic progression of human cells on the basis of four-dimensional image data. We use this model to integrate dynamic three-dimensional concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy(5). The approach taken here to generate a dynamic protein atlas of human cell division is generic; it can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types, and can be conceptually transferred to other cellular functions.
引用
收藏
页码:411 / +
页数:19
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