Developmental cell, 2002-07, Vol.3 (1), p.85-97
2002
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- Autor(en) / Beteiligte
- Titel
- aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation
- Ist Teil von
- Developmental cell, 2002-07, Vol.3 (1), p.85-97
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2002
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin. Human aph-1 and pen-2 partially rescue the C. elegans mutant phenotypes, demonstrating conserved functions. The human genes must be provided together to rescue the mutant phenotypes, and the inclusion of presenilin-1 improves rescue, suggesting that they interact closely with each other and with presenilin. RNAi-mediated inactivation of aph-1, pen-2, or nicastrin in cultured Drosophila cells reduces gamma-secretase cleavage of betaAPP and Notch substrates and reduces the levels of processed presenilin. aph-1 and pen-2, like nicastrin, are required for the activity and accumulation of gamma-secretase.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1534-5807Titel-ID: cdi_proquest_miscellaneous_71891104
- Format
- –
- Schlagworte
- Alzheimer Disease - genetics, Alzheimer Disease - metabolism, Amyloid beta-Protein Precursor - genetics, Amyloid beta-Protein Precursor - metabolism, Amyloid Precursor Protein Secretases, Animals, Aspartic Acid Endopeptidases, Caenorhabditis elegans, Caenorhabditis elegans Proteins - genetics, Caenorhabditis elegans Proteins - isolation & purification, Caenorhabditis elegans Proteins - metabolism, Cell Membrane - metabolism, Cell Membrane - ultrastructure, Cells, Cultured, Cloning, Molecular, Drosophila melanogaster, Drosophila Proteins, Endopeptidases - metabolism, Enhancer Elements, Genetic - genetics, Glucagon - metabolism, Glucagon-Like Peptide 1, Helminth Proteins - metabolism, Homeodomain Proteins - genetics, Homeodomain Proteins - isolation & purification, Homeodomain Proteins - metabolism, Humans, Intracellular Membranes - metabolism, Membrane Proteins - genetics, Membrane Proteins - isolation & purification, Membrane Proteins - metabolism, Molecular Sequence Data, Mutation - genetics, Peptide Fragments - metabolism, Presenilin-1, Protein Precursors - metabolism, Receptors, Notch, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Signal Transduction - genetics