The recycling (top, arrowheads) of CLR (red) back to the plasma membrane is blocked in cells lacking ECE-1 (bottom).
Peptidases on the cell surface cleave and thereby activate or inactivate small, extracellular peptides such as angiotensin. The enzymes also reside in internal compartments called endosomes, where their action is less apparent.
The new work shows that a peptidase called ECE-1 needs the low pH of the endosome to cleave several of its targets. One such peptide target was CGRP, which is released by cells during inflammation. Binding of CGRP to its receptor, CLR, induces pain signaling pathways in neurons. The peptide–receptor complex is then internalized into endosomes, which switches off the pain pathway.
Padilla and colleagues found that the internalized peptide/receptor was accompanied by ECE-1 into endosomes....
