Complex N-glycosylated form of nicastrin is stabilized and selectively bound to presenilin fragments

The transmembrane glycoprotein nicastrin is a component of presenilin (PS) protein complex that is involved in gamma-cleavage of betaAPP and site-3 cleavage of Notch. PS undergoes endoproteolysis, and the proteolytic fragments are incorporated into the high molecular weight protein complexes that are highly stabilized. Here we show that Endo H-resistant, N-glycosylated form of nicastrin (p150-NCT) is highly stabilized and selectively bound to PS fragments. Moreover, loss-of-function mutations of nicastrin inhibited formation of fully glycosylated p150-NCT as well as stabilization of nicastrin, suggesting that glycosylation and stabilization of nicastrin polypeptides are tightly correlated with its function. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.