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

作者：Hong Young Gi; Roh Seyun; Paik Donggi; Jeong Sangyun^*

来源：Molecules and Cells, 2017, 40(1): 73-81.

DOI：10.14348/molcells.2017.2294

• gamma-secretase
• Alzheimer's disease
• APPL
• Notch
• presenilin

The beta-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 beta-secretase catalytic component, presenilin, which lead to increased amyloid. peptide production, are responsible for early-onset familial Alzheimer's disease. beta-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 beta-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 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 in vivo reporter systems provide a powerful genetic tool to identify genes that modulate beta-secretase activity and/or APPL metabolism.

• 出版日期2017-1