UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

1-31-2017

Document Type

Article

Disciplines

Cell Biology | Molecular Biology

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 betapeptide 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.

Rights and Permissions

© Korean Society for Molecular and Cellular Biology. Citation: Mol Cells. 2017 Jan;40(1):73-81. Epub 2017 Jan 26. Link to article on publisher's site

DOI of Published Version

10.14348/molcells.2017.2294

Related Resources

Link to Article in PubMed

Keywords

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

Journal/Book/Conference Title

Molecules and cells

PubMed ID

28152299

Creative Commons License

Creative Commons Attribution-Noncommercial-Share Alike 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 License.

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