title: A combined binary interaction and phenotypic map of C. elegans cell polarity proteins.
abstract: The establishment of cell polarity is an essential process for the development of multicellular organisms and the functioning of cells and tissues. Here, we combine large-scale protein interaction mapping with systematic phenotypic profiling to study the network of physical interactions that underlies polarity establishment and maintenance in the nematode Caenorhabditis elegans. Using a fragment-based yeast two-hybrid strategy, we identified 439 interactions between 296 proteins, as well as the protein regions that mediate these interactions. Phenotypic profiling of the network resulted in the identification of 100 physically interacting protein pairs for which RNAi-mediated depletion caused a defect in the same polarity-related process. We demonstrate the predictive capabilities of the network by showing that the physical interaction between the RhoGAP PAC-1 and PAR-6 is required for radial polarization of the C. elegans embryo. Our network represents a valuable resource of candidate interactions that can be used to further our insight into cell polarization.
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Thijs
authors.initials: T
authors.lastname: Koorman
authors.affiliation: Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York 10016, USA.|Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Diana
authors.initials: D
authors.lastname: Klompstra
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van der Voet
authors.affiliation: Department of Medical Protein Research, VIB, 9000 Ghent, Belgium.|Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
authors.forename: Irma
authors.initials: I
authors.lastname: Lemmens
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: João J
authors.initials: JJ
authors.lastname: Ramalho
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Nieuwenhuize
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: van den Heuvel
authors.affiliation: Department of Medical Protein Research, VIB, 9000 Ghent, Belgium.|Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.affiliation: Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, NYU School of Medicine, New York, New York 10016, USA.|Department of Cell Biology, NYU School of Medicine, New York, New York 10016, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Nance
authors.affiliation: Division of Developmental Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH, Utrecht, The Netherlands.
authors.forename: Mike
authors.identifier: http://orcid.org/0000-0003-3966-4173
authors.initials: M
authors.lastname: Boxem
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein