Development of a Reporter System for In Vivo Monitoring of γ-Secretase Activity in Drosophila

• Published in: Molecules and cells Vol. 40; no. 1; pp. 73 - 81
• Main Authors: Hong, Young Gi, Roh, Seyun, Paik, Donggi, Jeong, Sangyun
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.01.2017; 한국분자세포생물학회
• Subjects: Amyloid Precursor Protein Secretases - analysis; Amyloid Precursor Protein Secretases - genetics; Amyloid Precursor Protein Secretases - metabolism; Animals; Drosophila - enzymology; Drosophila - genetics; Female; Immunohistochemistry; Male; Mutation; Receptors, Notch - metabolism; Signal Transduction; 생물학; Alzheimer’s disease; γ-secretase; APPL; presenilin; Notch
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2017.2294

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 the ortholog of human APP. Here, we created Notch- and APPL-based reporter systems for monitoring 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 the gain-of-function allele and suppressed by RNAi-mediated knockdown of . 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 both reporter systems provide a powerful genetic tool to identify genes that modulate γ-secretase activity and/or APPL metabolism.