Cellular membranes are important biological interfaces. Not only do they compartmentalize cells from the environment and organelles from each other, but they also act as signaling platforms. Accordingly, membrane proteins, which include for example receptors, ligands, cytokines, growth factors, transporters, enzymes, and adhesion proteins, have cardinal roles in signaling between cells. In fact, 30% of the human proteome are membrane proteins and they are also the target of many important drugs. The rhomboid-like superfamily comprises the rhomboid intramembrane serine proteases, which have membrane bilayer-embedded catalytic sites, and their pseudoprotease cousins, which lack active sites. By regulating other membrane proteins, members of this superfamily control many important biological processes. For example, rhomboid-like proteins can release membrane tethered signaling domains, regulate cellular homeostasis and quality control, and direct membrane trafficking. The diversity of rhomboid-like protein functions is becoming so wide that they can be viewed as multifunctional overseers of the membrane proteome. I will discuss both our latest work on rhomboid-like proteins, as well as the themes that are emerging about their mechanisms and role in disease.
Matthew Freeman (Sun,) studied this question.