Proprotein convertases (PCs) are big shots in the body because they snip and turn on numerous hormones, receptors, adhesion molecules, and other crucial proteins. Mesnard and Constam describe a new technique to track the activity of some of these ubiquitous but hard-to-study enzymes.

The targets of the nine PCs range from insulin to the blood pressure regulator renin to several proteins implicated in Alzheimer's disease. Cancer cells and pathogens such as HIV often co-opt the enzymes for nefarious ends. For example, PCs turn on matrix metalloproteinases that clear away extracellular matrix and allow cancer cells to spread. But the enzymes' widespread distribution and overlapping functions have made it difficult to tease out what jobs individual enzymes perform.

To simplify the task, Mesnard and Constam devised a method to determine when and where PCs are working. They fused yellow and blue fluorescent proteins to create a biosensor they call CLIP. When PCs are absent, the two colors remain together. But active PCs cut CLIP and separate the colors. Researchers can thus track PC activity inside a cell and at its surface, or even in whole tissues. Mesnard and Constam used the approach to find out when two PCs, Pace4 and Furin, switch on in early mouse embryos. The enzymes were on the job before the blastocyst implanted, earlier than expected. The researchers say that CLIP could improve drug design, allowing scientists to pin down where certain PCs are functioning in diseases and monitor the effectiveness of inhibitors dispatched to those sites.

J. Cell Biol.