Mapping the Polarity Interactome.

Interactions between proteins are an essential part of biology, and the desire to identify these interactions has led to the development of numerous technologies to systematically map protein-protein interactions at a large scale. As in most cellular processes, protein interactions are central to the control of cell polarity, and a full understanding of polarity will require comprehensive knowledge of the protein interactions involved. At its core, cell polarity is established through carefully regulated mutually inhibitory interactions between several groups of cortical proteins. While several interactions have been identified, the dynamics and molecular mechanisms that control these interactions are not well understood. Cell polarity also needs to be integrated with cellular processes including junction formation, cytoskeletal organization, organelle positioning, protein trafficking, and functional specialization of membrane domains. Moreover, polarized cells need to respond to external cues that coordinate polarity at the tissue level. Identifying the protein-protein interactions responsible for integrating polarity with all of these processes remains a major challenge, in part because the mechanisms of polarity control vary in different contexts and with developmental times. Because of their unbiased nature, systematic large-scale protein-protein interaction mapping approaches can be particularly helpful to identify such mechanisms. Here, we discuss methods commonly used to generate proteome-wide interactome maps, with an emphasis on advances in our understanding of cell polarity that have been achieved through application of such methods.