Systems survey of endocytosis by multiparametric image analysis

被引：335

作者：

Collinet, Claudio ^{[1
]}

Stoeter, Martin

Bradshaw, Charles R. ^{[1
]}

Samusik, Nikolay ^{[1
]}

Rink, Jochen C.

Kenski, Denise

Habermann, Bianca ^{[1
]}

Buchholz, Frank ^{[1
]}

Henschel, Robert ^{[2
]}

Mueller, Matthias S. ^{[2
]}

Nagel, Wolfgang E. ^{[2
]}

Fava, Eugenio

Kalaidzidis, Yannis ^{[1
,3
]}

Zerial, Marino ^{[1
]}

机构：

[1] MPI CBG, Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany

[2] Tech Univ Dresden, Ctr Informat Serv & High Performance Comp ZIH, D-01062 Dresden, Germany

[3] Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia

来源：

NATURE | 2010年 / 464卷 / 7286期

关键词：

MEDIATED ENDOCYTOSIS; SIGNAL-TRANSDUCTION; CELL BIOLOGY; ENDOSOMES; CYTOKINESIS; SPECIFICITY; MECHANISMS; PROTEINS; GRADIENT; SCREEN;

D O I：

10.1038/nature08779

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：

Endocytosis is a complex process fulfilling many cellular and developmental functions. Understanding how it is regulated and integrated with other cellular processes requires a comprehensive analysis of its molecular constituents and general design principles. Here, we developed a new strategy to phenotypically profile the human genome with respect to transferrin (TF) and epidermal growth factor (EGF) endocytosis by combining RNA interference, automated high-resolution confocal microscopy, quantitative multiparametric image analysis and high-performance computing. We identified several novel components of endocytic trafficking, including genes implicated in human diseases. We found that signalling pathways such as Wnt, integrin/cell adhesion, transforming growth factor (TGF)-beta and Notch regulate the endocytic system, and identified new genes involved in cargo sorting to a subset of signalling endosomes. A systems analysis by Bayesian networks further showed that the number, size, concentration of cargo and intracellular position of endosomes are not determined randomly but are subject to specific regulation, thus uncovering novel properties of the endocytic system.

引用

页码：243 / U123

页数：8

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