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
-
- Mutation/genetics
- Animals
- Glucagon-Like Peptide 1
- Endopeptidases/metabolism*
- Receptors, Notch
- Glucagon/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/isolation & purification*
- Membrane Proteins/metabolism*
- Enhancer Elements, Genetic/genetics
- Drosophila Proteins
- Drosophila melanogaster
- Presenilin-1
- Humans
- Intracellular Membranes/metabolism
- Peptide Fragments/metabolism
- Caenorhabditis elegans
- Signal Transduction/genetics
- Cells, Cultured
- Molecular Sequence Data
- Protein Precursors/metabolism
- Amyloid beta-Protein Precursor/genetics
- Amyloid beta-Protein Precursor/metabolism*
- Aspartic Acid Endopeptidases
- Cell Membrane/metabolism*
- Cell Membrane/ultrastructure
- Cloning, Molecular
- Amyloid Precursor Protein Secretases
- Helminth Proteins/metabolism
- Alzheimer Disease/genetics
- Alzheimer Disease/metabolism
- Sequence Homology, Nucleic Acid
- Sequence Homology, Amino Acid
- Caenorhabditis elegans Proteins/genetics
- Caenorhabditis elegans Proteins/isolation & purification*
- Caenorhabditis elegans Proteins/metabolism
- Homeodomain Proteins/genetics
- Homeodomain Proteins/isolation & purification*
- Homeodomain Proteins/metabolism
- 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