2. Academic Validation
  3. Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing

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

  • Nature. 2000 Sep 7;407(6800):48-54. doi: 10.1038/35024009.
G Yu 1,  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
Affiliations

Affiliation

  • 1 Centre for Research in Neurodegenerative Diseases, Toronto Western Hospital, and Department of Medicine (Neurology), University of Toronto, Ontario, Canada.
PMID: 10993067 DOI: 10.1038/35024009
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.

Figures