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Development of a Reporter System for In Vivo Monitoring of γ-Secretase Activity in Drosophila
홍영기,노세윤,백동기,정상윤 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.1
The -secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the -amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the -secretase catalytic component, presenilin, which lead to increased amyloid -peptide production, are responsible for early-onset familial Alzheimer’s disease. -amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of -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 Notch gain-of-function allele and suppressed by RNAi-mediated knockdown of presenilin. Furthermore, we find that apoptosis partly con-tributes 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 in vivo reporter systems provide a pow-erful genetic tool to identify genes that modulate -secretase activity and/or APPL metabolism.