Mechanisms of ligand‐mediated inhibition in Notch signaling activity in Drosophila

The transmembrane proteins Delta and Serrate act as ligands for the signaling receptor Notch. In addition to this activating role, Delta and Serrate can also inhibit Notch signaling activity. This inhibitory effect is concentration-dependent and appears to be evolutionarily conserved. In characterizing the underlying cellular mechanisms of the ligand inhibitory effect, we can confirm that ligand-mediated inhibition of Notch signaling can occur as a cell autonomous process (cis-inhibition) and that ligand-mediated inhibition prevents a step in Notch signaling activation early enough to suppress Notch ectodomain shedding.