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In this issue |
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Intramembrane cleavage of receptors such as Notch and amyloid precursor
protein (APP) is mediated by 
-secretase – a complex thought to
contain presenilin and nicastrin. Presenilin is essential for
-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 -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 -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.
Related articles in JCS:
-Secretase activity requires the presenilin-dependent trafficking of nicastrin through the Golgi apparatus but not its complex glycosylation
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