The polarity sub-network in the yeast network of protein-protein interactions

Rare, but highly connected, hub proteins subdivide hierarchically global networks of interacting proteins into modular clusters. Most biological research, however, focuses on functionally defined sub-networks. Thus, it is important to know whether the sub-networks retain the same topology of the global networks, from which they derive. To address this issue, we have analyzed the protein-protein interaction sub-network that participates in the polarized growth of the budding yeast Saccharomyces cerevisiae and that is derived from the global network of this model organism. We have observed that, in contrast to global networks, the distribution of connectivity k (i.e., the number of interactions per protein) does not follow a power law, but decays exponentially, which reflects the local absence of hub proteins. Nonetheless, far from being randomly organized, the polarity sub-network can be subdivided into functional modules. In addition, most non-hub connector proteins, besides ensuring communications among modules, are linked mutually and contribute to the formation of the polarisome, a structure that coordinates actin assembly with polarized growth. These findings imply that identifying critical proteins within sub-networks (e.g., for the aim of targeted therapy) requires searching not only for hubs but also for key non-hub connectors, which might remain otherwise unnoticed due to their relatively low connectivity.