Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing.
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.
Mesh Terms:
Amino Acid Sequence, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor, Animals, Aspartic Acid Endopeptidases, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA, Complementary, Endopeptidases, Humans, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Presenilin-1, Presenilin-2, Receptors, Notch, Sequence Homology, Amino Acid, Signal Transduction, Transfection
Amino Acid Sequence, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor, Animals, Aspartic Acid Endopeptidases, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA, Complementary, Endopeptidases, Humans, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Presenilin-1, Presenilin-2, Receptors, Notch, Sequence Homology, Amino Acid, Signal Transduction, Transfection
Nature
Date: Sep. 07, 2000
PubMed ID: 10993067
View in: Pubmed Google Scholar
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