Delta cells (blue) pull on the Notch cell to remove and take up the Notch extracellular domain (green).

Notch's neighbors are tearing it apart. On page 445, Nichols et al. show that endocytosis of a ligand on one cell pulls apart its Notch receptor on an adjacent cell, leaving behind an activation-susceptible receptor remnant.

Dormant Notch on the cell surface must be cleaved into a free intracellular domain that can travel to the nucleus to activate gene expression. Three proteases are known to trim Notch. The first, furin, cleaves before the receptor reaches the plasma membrane and leaves Notch in two pieces that are held together by noncovalent bonds.

The next two cleavages, by ADAM and then γ-secretase, occur after Notch binds a ligand such as Delta on an adjacent cell. Endocytosis in the Delta cell is necessary to activate Notch signaling in the...

The Rockefeller University Press
2007
The Rockefeller University Press
2007
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