The intricate web of protein–protein interactions in the cell is now revealing its secrets to us, due to the development of high-throughput two-hybrid screening. Reporting in the Journal of Cell Biology, Drees and colleagues now describe the results of their screen for cell polarity proteins.

To target this type of protein, Drees and colleagues used as bait 68 proteins known to mediate cell polarity, ranging from Rho-type GTPases to proteins involved in secretion. The result was 128 new protein–protein interactions, 44 of which involve proteins of unknown function. So what does this tell us about how the polarity factors are weaved together?

One important outcome is that new connections were made, both between signalling pathways — for example, the Rho1 and Cdc42 effector pathways — and between distinct processes, such as the assembly of actin and the morphogenesis checkpoint. To confirm some of these interactions, the authors fused factors to yellow fluorescent protein and looked at their subcellular localization.

Given that many of these factors have mammalian homologues, these interactions have implications for polarity in diverse cell types, but there is still much to learn. The next step will be to use genetic and biochemical tools to ask when and where these factors meet in the cell and how the information flows through this complex web.