ArticleMolecular and cellular biology2010
In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Pathological Defects in a Drosophila Model of Alzheimer's Disease and Beneficial Effects of the Natural Product Lisosan G.Biomolecules · 2024Article
- Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.International journal of molecular sciences · 2024Review
- The amyloid precursor protein intracellular domain induces sleep disruptions and its nuclear localization fluctuates in circadian pacemaker neurons in Drosophila and mice.Neurobiology of disease · 2024Article
- γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.Developmental cell · 2022Article
- Expression of a human variant of CHMP2B linked to neurodegeneration in Drosophila external sensory organs leads to cell fate transformations associated with increased Notch activity.Developmental neurobiology · 2020Article
- Farnesylated heat shock protein 40 is a component of membrane-bound RISC inThe Journal of biological chemistry · 2018Article
- Autophagy maintains stem cells and intestinal homeostasis in Drosophila.Scientific reports · 2018Article
- Development of a Reporter System forMolecules and cells · 2017Article
- Stem-cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila.Disease models & mechanisms · 2016Article
- Analysis of Amyloid Precursor Protein Function in Drosophila melanogaster.Frontiers in molecular neuroscience · 2016Review
- Review
- Article
- Presenilin controls kinesin-1 and dynein function during APP-vesicle transport in vivo.Human molecular genetics · 2013Article
- Sanpodo controls sensory organ precursor fate by directing Notch trafficking and binding γ-secretase.The Journal of cell biology · 2013Article
- Hibris, a Drosophila nephrin homolog, is required for presenilin-mediated Notch and APP-like cleavages.Developmental cell · 2012Article
- Analysis of amyloid precursor protein function in Drosophila melanogaster.Experimental brain research · 2012Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The intramembrane aspartyl protease gamma-secretase plays a fundamental role in several signaling pathways involved in cellular differentiation and has been linked with a variety of human diseases, including Alzheimer's disease. Here, we describe a transgenic Drosophila model for in vivo-reconstituted gamma-secretase, based on expression of epitope-tagged versions of the four core gamma-secretase components, Presenilin, Nicastrin, Aph-1, and Pen-2. In agreement with previous cell culture and yeast studies, coexpression of these four components promotes the efficient assembly of mature, proteolytically active gamma-secretase. We demonstrate that in vivo-reconstituted gamma-secretase has biochemical properties and a subcellular distribution resembling those of endogenous gamma-secretase. However, analysis of the cleavage of alternative substrates in transgenic-fly assays revealed unexpected functional differences in the activity of reconstituted gamma-secretase toward different substrates, including markedly reduced cleavage of some APP family members compared to cleavage of the Notch receptor. These findings indicate that in vivo under physiological conditions, additional factors differentially modulate the activity of gamma-secretase toward its substrates. Thus, our approach for the first time demonstrates the overall functionality of reconstituted gamma-secretase in a multicellular organism and the requirement for substrate-specific factors for efficient in vivo cleavage of certain substrates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.