Endocytic routes to Notch activation

► Endosomal sorting of Notch can down or upregulate signalling. ► Endocytosis of Notch may contribute to full signalling levels following ligand-activation. ► Endocytosis is essential for Notch activation by ligand-independent mechanisms. ► Notch activation can occur at different locations in the endosomal pathway. ► Combination of Notch signalling mechanisms provides developmental robustness.