Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Development of a Reporter System for In Vivo Monitoring of γ-Secretase Activity in Drosophila

  • Hong, Young Gi (Department of Molecular Biology, Chonbuk National University) ;
  • Roh, Seyun (Department of Molecular Biology, Chonbuk National University) ;
  • Paik, Donggi (Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School) ;
  • Jeong, Sangyun (Department of Molecular Biology, Chonbuk National University)
  • Received : 2016.12.02
  • Accepted : 2016.12.28
  • Published : 2017.01.31
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Abstract

The ${\gamma}$-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the ${\beta}$-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the ${\gamma}$-secretase catalytic component, presenilin, which lead to increased amyloid ${\beta}$-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 ${\gamma}$-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 ${\gamma}$-secretase activity and/or APPL metabolism.

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