PUBLICATION
aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation
- Authors
- Francis, R., McGrath, G., Zhang, J., Ruddy, D.A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M.C., Parks, A.L., Xu, W., Li, J., Gurney, M., Myers, R.L., Himes, C.S., Hiebsch, R., Ruble, C., Nye, J.S., and Curtis, D.
- ID
- ZDB-PUB-040113-1
- Date
- 2002
- Source
- Developmental Cell 3(1): 85-97 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/isolation & purification*
- Caenorhabditis elegans Proteins/metabolism
- Amyloid Precursor Protein Secretases
- Drosophila Proteins
- Glucagon-Like Peptide 1
- Humans
- Membrane Proteins/genetics
- Membrane Proteins/isolation & purification*
- Membrane Proteins/metabolism*
- Amyloid beta-Protein Precursor/genetics
- Amyloid beta-Protein Precursor/metabolism*
- Receptors, Notch
- Cells, Cultured
- Peptide Fragments/metabolism
- Cloning, Molecular
- Mutation/genetics
- Endopeptidases/metabolism*
- Enhancer Elements, Genetic/genetics
- Glucagon/metabolism
- Aspartic Acid Endopeptidases
- Protein Precursors/metabolism
- Intracellular Membranes/metabolism
- Animals
- Sequence Homology, Amino Acid
- Homeodomain Proteins/genetics
- Homeodomain Proteins/isolation & purification*
- Homeodomain Proteins/metabolism
- Caenorhabditis elegans
- Molecular Sequence Data
- Helminth Proteins/metabolism
- Presenilin-1
- Sequence Homology, Nucleic Acid
- Cell Membrane/metabolism*
- Cell Membrane/ultrastructure
- Alzheimer Disease/genetics
- Alzheimer Disease/metabolism
- Drosophila melanogaster
- Signal Transduction/genetics
- PubMed
- 12110170 Full text @ Dev. Cell
Citation
Francis, R., McGrath, G., Zhang, J., Ruddy, D.A., Sym, M., Apfeld, J., Nicoll, M., Maxwell, M., Hai, B., Ellis, M.C., Parks, A.L., Xu, W., Li, J., Gurney, M., Myers, R.L., Himes, C.S., Hiebsch, R., Ruble, C., Nye, J.S., and Curtis, D. (2002) aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Developmental Cell. 3(1):85-97.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping