Development of a Reporter System forIn VivoMonitoring of γ-Secretase Activity inDrosophila.
The γ-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the β-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the γ-secretase catalytic component, presenilin, which lead to increased amyloid βpeptide production, are responsible for early-onset familial Alzheimer's disease. β-amyloid protein precursor-like (APPL) is theDrosophilaortholog of human APP. Here, we created Notch- and APPL-basedDrosophilareporter systems forin vivomonitoring of γ-secretase activity. Ectopic expression of the Notch- and APPL-based chimeric reporters in wings results in vein truncation phenotypes. Reporter-mediated vein truncation phenotypes are enhanced by theNotchgain-of-function allele and suppressed by RNAi-mediated knockdown ofpresenilin. Furthermore, we find that apoptosis partly contributes to the vein truncation phenotypes of the APPL-based reporter, but not to the vein truncation phenotypes of the Notch-based reporter. Taken together, these results suggest that bothin vivoreporter systems provide a powerful genetic tool to identify genes that modulate γ-secretase activity and/or APPL metabolism.
Department of Molecular Biology, Chonbuk National University, Jeonju 54896, Korea.
Young Gi
YG
Hong
Department of Molecular Biology, Chonbuk National University, Jeonju 54896, Korea.
Seyun
S
Roh
Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Donggi
D
Paik
Department of Molecular Biology, Chonbuk National University, Jeonju 54896, Korea.
Sangyun
S
Jeong
D053829:Amyloid Precursor Protein Secretases / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009154:Mutation; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction
D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases
APPL; Alzheimer’s disease; Notch; presenilin; γ-secretase