High Iron Diamine and Metachromatic Staining
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The final, regulated intramembrane proteolysis (RIP) step in NOTCH activation is carried out by the γ-secretase complex. This multi-protein complex is embedded in the membrane and includes presenilin (which provides the catalytic aspartyl protease activity), nicastrin, Aph-1, and Pen-2. After ligand binding and the first cleavage by ADAM metalloprotease, γ-secretase cleaves the transmembrane stub of NOTCH within the lipid bilayer, releasing the NOTCH Intracellular Domain (NICD) into the cytoplasm.
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