γ-secretase-mediated proteolysis in cell-surface-receptor signalling

Many cell-surface receptors transmit signals to the nucleus through complex protein cascades. By contrast, the Notch signalling pathway uses a relatively direct mechanism, in which the intracellular domain of the receptor is liberated by intramembrane cleavage and translocates to the nucleus. This critical cleavage is mediated by the gamma-secretase complex, and new findings reveal that this mechanism is used by various receptors, although many questions remain about the biochemical details.