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Interference of human and Drosophila APP and APP‐like proteins with PNS development in Drosophila
Author(s) -
Merdes Gunter,
Soba Peter,
Loewer Alexander,
Bilic Michaela V,
Beyreuther Konrad,
Paro Renato
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600413
Subject(s) - biology , drosophila (subgenus) , rna interference , drosophila melanogaster , drosophilidae , interference (communication) , genetics , microbiology and biotechnology , gene , rna , electrical engineering , engineering , channel (broadcasting)
The view that only the production and deposition of Aβ plays a decisive role in Alzheimer's disease has been challenged by recent evidence from different model systems, which attribute numerous functions to the amyloid precursor protein (APP). To investigate the potential cellular functions of APP and its paralogs, we use transgenic Drosophila as a model. Upon overexpression of the APP‐family members, transformations of cell fates during the development of the peripheral nervous system were observed. Genetic analysis showed that APP, APLP1 and APLP2 induce Notch gain‐of‐function phenotypes, identified Numb as a potential target and provided evidence for a direct involvement of Disabled and Neurotactin in the induction of the phenotypes. The severity of the induced phenotypes not only depended on the dosage and the particular APP‐family member but also on particular domains of the molecules. Studies with Drosophila APPL confirmed the results obtained with human proteins and the analysis of flies mutant for the appl gene further supports an involvement of APP‐family members in neuronal development and a crosstalk between the APP family and Notch.