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Nature. 2000 Sep 7;407(6800):48-54.

Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing.

Author information

1
Centre for Research in Neurodegenerative Diseases, Toronto Western Hospital, and Department of Medicine (Neurology), University of Toronto, Ontario, Canada.

Abstract

Nicastrin, a transmembrane glycoprotein, forms high molecular weight complexes with presenilin 1 and presenilin 2. Suppression of nicastrin expression in Caenorhabditis elegans embryos induces a subset of notch/glp-1 phenotypes similar to those induced by simultaneous null mutations in both presenilin homologues of C. elegans (sel-12 and hop-1). Nicastrin also binds carboxy-terminal derivatives of beta-amyloid precursor protein (betaAPP), and modulates the production of the amyloid beta-peptide (A beta) from these derivatives. Missense mutations in a conserved hydrophilic domain of nicastrin increase A beta42 and A beta40 peptide secretion. Deletions in this domain inhibit A beta production. Nicastrin and presenilins are therefore likely to be functional components of a multimeric complex necessary for the intramembranous proteolysis of proteins such as Notch/GLP-1 and betaAPP.

PMID:
10993067
DOI:
10.1038/35024009
[Indexed for MEDLINE]

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