The ability to polarize is a fundamental cellular property, required for processes such as cell migration and asymmetric cell division, and for the specification of functionally distinct domains. Several key determinants of cell polarity have been identified, including the Par, Crumbs, and Scribble groups of cortical polarity regulators. However, we know comparatively little of the mechanisms through which cortical polarity is integrated with cellular events such as cytoskeletal rearrangement, organization of a polarized trafficking machinery, and functional specialization of membrane domains. A full understanding of polarity establishment will require a comprehensive knowledge of the proteins involved in this process and the molecular interactions between them.
Here, we study the network of physical interactions that underlies polarity establishment in the nematode Caenorhabditis elegans using a combination of large-scale yeast two-hybrid screens and phenotypic profiling. 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.