| First Author | Yu G | Year | 2000 |
| Journal | Nature | Volume | 407 |
| Issue | 6800 | Pages | 48-54 |
| PubMed ID | 10993067 | Mgi Jnum | J:64305 |
| Mgi Id | MGI:1889081 | Doi | 10.1038/35024009 |
| Citation | Yu G, et al. (2000) Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing [see comments]. Nature 407(6800):48-54 |
| abstractText | 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. |
