Intramembrane cleavage of receptors such as Notch and amyloid precursor protein (APP) is mediated by γ-secretase – a complex thought to contain presenilin and nicastrin. Presenilin is essential forγ-secretase activity but does not colocalize with it, concentrating instead in the ER. This `spatial paradox' remains a puzzle – as does presenilin's relationship with nicastrin, which probably stabilizes presenilin. Bart De Strooper and co-workers have investigated the relationship between these two proteins by studying maturation of nicastrin in wild-type and presenilin-deficient cells and the effects on γ-secretase activity(see p. 1127). They find that nicastrin undergoes complex glycosylation in the Golgi but that this does not occur in cells lacking presenilin 1 and presenilin 2. They go on to show that this glycosylation is not required for γ-secretase activity or for association of nicastrin with presenilin but is required for transport of nicastrin to the cell surface. The authors also observe that presenilin and nicastrin colocalize to some extent. Their findings thus not only indicate that presenilin is important for nicastrin trafficking but go some way to resolving the spatial paradox, since they suggest small amounts of presenilin accompany nicastrin beyond the ER.
The presenilin paradox resolved?
The presenilin paradox resolved?. J Cell Sci 15 March 2003; 116 (6): e605. doi:
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