| Literature DB >> 10993067 |
G Yu1, M Nishimura, S Arawaka, D Levitan, L Zhang, A Tandon, Y Q Song, E Rogaeva, F Chen, T Kawarai, A Supala, L Levesque, H Yu, D S Yang, E Holmes, P Milman, Y Liang, D M Zhang, D H Xu, C Sato, E Rogaev, M Smith, C Janus, Y Zhang, R Aebersold, L S Farrer, S Sorbi, A Bruni, P Fraser, P St George-Hyslop.
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.Entities:
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Year: 2000 PMID： 10993067 DOI： 10.1038/35024009
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962