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Mol Cells. 2017 Jan;40(1):73-81. doi: 10.14348/molcells.2017.2294. Epub 2017 Jan 26.

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

Author information

  • 1Department of Molecular Biology, Chonbuk National University, Jeonju 54896, Korea.
  • 2Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

Abstract

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 Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo 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 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 γ-secretase activity and/or APPL metabolism.

KEYWORDS:

APPL; Alzheimer’s disease; Notch; presenilin; γ-secretase

PMID:
28152299
DOI:
10.14348/molcells.2017.2294
[PubMed - in process]
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