NDLI: Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype.

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Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype.

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Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Brückner, B. Czech, C. Masters, C. L. Paro, R. Fossgreen, A. Beyreuther, K.
Description	Author Affiliation: Fossgreen A ( Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.);
Abstract	The importance of the amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease (AD) became apparent through the identification of distinct mutations in the APP gene, causing early onset familial AD with the accumulation of a 4-kDa peptide fragment (betaA4) in amyloid plaques and vascular deposits. However, the physiological role of APP is still unclear. In this work, Drosophila melanogaster is used as a model system to analyze the function of APP by expressing wild-type and various mutant forms of human APP in fly tissue culture cells as well as in transgenic fly lines. After expression of full-length APP forms, secretion of APP but not of betaA4 was observed in both systems. By using SPA4CT, a short APP form in which the signal peptide was fused directly to the betaA4 region, transmembrane domain, and cytoplasmic tail, we observed betaA4 release in flies and fly-tissue culture cells. Consequently, we showed a gamma-secretase activity in flies. Interestingly, transgenic flies expressing full-length forms of APP have a blistered-wing phenotype. As the wing is composed of interacting dorsal and ventral epithelial cell layers, this phenotype suggests that human APP expression interferes with cell adhesion/signaling pathways in Drosophila, independently of betaA4 generation.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	95
Language	English
Publisher	National Academy of Sciences
Publisher Date	1998-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Amyloid Beta-Protein Precursor Genetics Drosophila Melanogaster Endopeptidases Gene Expression Regulation Genes, Insect Amyloid Precursor Protein Secretases Animals Animals, Genetically Modified Aspartic Acid Endopeptidases Cell Adhesion Phenotype Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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