ArticleThe Journal of cell biology2015
Physical and functional interaction between the α- and γ-secretases: A new model of regulated intramembrane proteolysis.
Article in The Journal of cell biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Lysosomal protease-mediated APP degradation is pH-dependent, mutation-sensitive, and facilitates tau proteolysis.Molecular neurodegeneration advances · 2026Article
- Dynamic association of the intramembrane proteases SPPL2a/b and their substrates with tetraspanin-enriched microdomains.iScience · 2023Article
- Identification of the Aβ37/42 peptide ratio in CSF as an improved Aβ biomarker for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- Preferential Involvement of BRCA1/BARD1, Not Tip60/Fe65, in DNA Double-Strand Break Repair in Presenilin-1 P117L Alzheimer Models.Neural plasticity · 2022Article
- Analysis of the Conditions That Affect the Selective Processing of Endogenous Notch1 by ADAM10 and ADAM17.International journal of molecular sciences · 2021Article
- Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.iScience · 2021Article
- New insights into the molecular mechanisms of axon guidance receptor regulation and signaling.Current topics in developmental biology · 2021Review
- Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface.eLife · 2020Article
- Knock-in rats with homozygousThe Journal of biological chemistry · 2020Article
- Live-cell monitoring of protein localization to membrane rafts using protein-fragment complementation.Bioscience reports · 2020Article
- Reciprocal modulation between amyloid precursor protein and synaptic membrane cholesterol revealed by live cell imaging.Neurobiology of disease · 2019Article
- A cellular complex of BACE1 and γ-secretase sequentially generates Aβ from its full-length precursor.The Journal of cell biology · 2019Article
- Emerging Alternative Proteinases in APP Metabolism and Alzheimer's Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP.Frontiers in aging neuroscience · 2019Review
- Synapsin 1 promotes Aβ generation via BACE1 modulation.PloS one · 2019Article
- Review
- Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.The EMBO journal · 2018Review
- The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) undergoes rapid, postlysis autocatalytic degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Visualization of Alzheimer's Disease Related α-/β-/γ-Secretase Ternary Complex by Bimolecular Fluorescence Complementation Based Fluorescence Resonance Energy Transfer.Frontiers in molecular neuroscience · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Many single-transmembrane proteins are sequentially cleaved by ectodomain-shedding α-secretases and the γ-secretase complex, a process called regulated intramembrane proteolysis (RIP). These cleavages are thought to be spatially and temporally separate. In contrast, we provide evidence for a hitherto unrecognized multiprotease complex containing both α- and γ-secretase. ADAM10 (A10), the principal neuronal α-secretase, interacted and cofractionated with γ-secretase endogenously in cells and mouse brain. A10 immunoprecipitation yielded γ-secretase proteolytic activity and vice versa. In agreement, superresolution microscopy showed that portions of A10 and γ-secretase colocalize. Moreover, multiple γ-secretase inhibitors significantly increased α-secretase processing (r = -0.86) and decreased β-secretase processing of β-amyloid precursor protein. Select members of the tetraspanin web were important both in the association between A10 and γ-secretase and the γ → α feedback mechanism. Portions of endogenous BACE1 coimmunoprecipitated with γ-secretase but not A10, suggesting that β- and α-secretases can form distinct complexes with γ-secretase. Thus, cells possess large multiprotease complexes capable of sequentially and efficiently processing transmembrane substrates through a spatially coordinated RIP mechanism.
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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.