A new way to explore the world of extracellular protein interactions.

Eukaryotic genomes encode large numbers of proteins that are either secreted or have exposed extracellular domains. It is highly likely that these proteins facilitate many important biological processes: however, as yet, most remain uncharacterized. Progress in this area of research has been impaired by the lack of a robust screening system that can be used to investigate interactions between large numbers of different extracellular proteins. In this issue, Bushell et al. introduce AVEXIS (avidity-based extracellular interaction screen), a high-throughput screening procedure, which can be used to identify even weak extracellular protein interactions with extremely high confidence. This assay represents an important development in the field of network biology. By combining data from the AVEXIS system with data produced by classical or variant yeast two-hybrid methods, it will be possible to assemble binary protein interaction networks that connect extracellular and intracellular processes. This information will dramatically increase our ability to understand a wide range of physiological processes and facilitate the development of better therapeutic strategies.