Regulation of Notch Signaling Through Intracellular Transport

The highly conserved Notch-signaling pathway performs a central role in cell differentiation, survival, and proliferation. A major mechanism by which cells modulate signaling is by controlling the intracellular transport itinerary of Notch. Indeed, Notch removal from the cell surface and its targeting to the lysosome for degradation is one way in which Notch activity is downregulated since it limits receptor exposure to ligand. In contrast, Notch-signaling capacity is maintained through repeated rounds of receptor recycling and redelivery of Notch to the cell surface from endosomal stores. This review discusses the molecular mechanisms by which Notch transit through the endosome is controlled and how various intracellular sorting decisions are thought to impact signaling activity.