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

ABSTRACT: 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 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 ?-secretase activity and/or APPL metabolism.

SUBMITTER: Hong YG 

PROVIDER: S-EPMC5303891 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature