Cell Polarity and Notch Signaling: Linked by the E3 Ubiquitin Ligase Neuralized?

Notch is a mechanosensitive receptor that requires direct cell–cell contact for its activation. Both the strength and the range of notch signaling depend on the size and geometry of the contact sites between cells. These properties of cell–cell contacts in turn depend on cell shape and polarity. At the molecular level, the E3 ubiquitin ligase Neuralized (Neur) links receptor activation with epithelial cell remodeling. Neur regulates the endocytosis of the Notch ligand Delta (Dl), hence Notch activation. It also targets the apical polarity protein Stardust (Sdt) to promote the endocytosis of the Crumbs complex, thereby contributing to epithelium remodeling. Here, we review the interplay between Notch signaling and cell polarity and discuss the possible significance of linking Notch signaling with epithelial cell polarity via a common regulator.

Notch receptor activation depends on direct cell–cell contacts that in turn depends on cell shape and cellular polarity. The size and geometry of cell–cell contacts have an impact on the strength and range of signaling. The E3 ubiquitin ligase Neuralized regulates the endocytosis and signaling activity of Delta. The activity of Neuralized is tightly regulated during development. Neuralized also modulates epithelial cell polarity by targeting the apical polarity protein Stardust and by promoting the endocytosis of Crumbs. Thus, the cell-specific expression of Neuralized (cell in orange) couples Notch receptor activation (high level of Notch activity in cells next to the Neur-expressing cell) with cell polarity regulation in epithelia (loss of the apical domain in the orange cell).

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