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A Hierarchical Map of Regulatory Genetic Interactions in Membrane Trafficking

Liberali, Prisca ; Snijder, Berend ; Pelkmans, Lucas

Cell, June 5, 2014, Vol.157(6), p.1473 [Peer Reviewed Journal]

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  • Title:
    A Hierarchical Map of Regulatory Genetic Interactions in Membrane Trafficking
  • Author: Liberali, Prisca ; Snijder, Berend ; Pelkmans, Lucas
  • Subjects: Genetic Research – Analysis ; Cells (Biology) – Analysis
  • Is Part Of: Cell, June 5, 2014, Vol.157(6), p.1473
  • Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/j.cell.2014.04.029 Byline: Prisca Liberali [prisca.liberali@uzh.ch] (1,*), Berend Snijder (1,2), Lucas Pelkmans [lucas.pelkmans@imls.uzh.ch] (1,**) Highlights * 13 image-based RNAi screens of the endocytic membrane system are on http://www.endocytome.org(http://www.endocytome.org) * Unbiased analysis reveals emergent properties and patterns of coregulation * First map of hierarchical interactions between kinases and core machinery determined * Hierarchical interactions also exist in yeast and show principles of regulation Summary Endocytosis is critical for cellular physiology and thus is highly regulated. To identify regulatory interactions controlling the endocytic membrane system, we conducted 13 RNAi screens on multiple endocytic activities and their downstream organelles. Combined with image analysis of thousands of single cells per perturbation and their cell-to-cell variability, this created a high-quality and cross-comparable quantitative data set. Unbiased analysis revealed emergent properties of the endocytic membrane system and how its complexity evolved and distinct programs of regulatory control that coregulate specific subsets of endocytic uptake routes and organelle abundances. We show that these subset effects allow the mapping of functional regulatory interactions and their interaction motifs between kinases, membrane-trafficking machinery, and the cytoskeleton at a large scale, some of which we further characterize. Our work presents a powerful approach to identify regulatory interactions in complex cellular systems from parallel single-gene or double-gene perturbation screens in human cells and yeast. Author Affiliation: (1) Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland * Corresponding author Article History: Received 12 September 2013; Revised 30 January 2014; Accepted 10 April 2014 (miscellaneous) Published: June 5, 2014 (footnote)2 Present address: CeMM-Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
  • Language: English
  • Identifier: ISSN: 0092-8674 ; DOI: 10.1016/j.cell.2014.04.029

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