ArticleThe Journal of biological chemistry2016
Presenilin 1 and Presenilin 2 Target γ-Secretase Complexes to Distinct Cellular Compartments.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 65 citations in OpenAlex.
- Lysosomal homeostasis at the crossroads of neurodegeneration.The Journal of clinical investigation · 2026Review
- Evidence that cholinergic mechanisms contribute to hyperexcitability at early stages in Alzheimer's disease.Frontiers in dementia · 2025Review
- The pathogenicity of PSEN2 variants is tied to Aβ production and homology to PSEN1.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer's disease-relevant brain circuits.Nature communications · 2024Article
- Inhibition of the NOTCH and mTOR pathways by nelfinavir as a novel treatment for T cell acute lymphoblastic leukemia.International journal of oncology · 2023Article
- APP-BACE1 Interaction and Intracellular Localization Regulate Aβ Production in iPSC-Derived Cortical Neurons.Cellular and molecular neurobiology · 2023Article
- Converging links between adult-onset neurodegenerative Alzheimer's disease and early life neurodegenerative neuronal ceroid lipofuscinosis?Neural regeneration research · 2023Review
- Different transmembrane domains determine the specificity and efficiency of the cleavage activity of the γ-secretase subunit presenilin.The Journal of biological chemistry · 2023Article
- Endosome and Lysosome Membrane Properties Functionally Link to γ-Secretase in Live/Intact Cells.Sensors (Basel, Switzerland) · 2023Article
- Regulation of Ryanodine Receptor-Dependent Neurotransmitter Release by AIP, Calstabins, and Presenilins.Advances in neurobiology · 2023Article
- Proteolytically generated soluble Tweak Receptor Fn14 is a blood biomarker for γ-secretase activity.EMBO molecular medicine · 2022Article
- Article
- Presenilin/γ-Secretase Activity Is Located in Acidic Compartments of Live Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The Potential of Gamma Secretase as a Therapeutic Target for Cardiac Diseases.Journal of personalized medicine · 2021Review
- Mechanism of Cellular Formation and In Vivo Seeding Effects of Hexameric β-Amyloid Assemblies.Molecular neurobiology · 2021Article
- Review
- Importance of γ-secretase in the regulation of liver X receptor and cellular lipid metabolism.Life science alliance · 2020Article
- RIP at the Synapse and the Role of Intracellular Domains in Neurons.Neuromolecular medicine · 2020Review
- Loss of presenilin 2 age-dependently alters susceptibility to acute seizures and kindling acquisition.Neurobiology of disease · 2020Article
- Signaling Functions of Intramembrane Aspartyl-Proteases.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-Secretase complexes achieve the production of amyloid peptides playing a key role in Alzheimer disease. These proteases have many substrates involved in important physiological functions. They are composed of two constant subunits, nicastrin and PEN2, and two variable ones, presenilin (PS1 or PS2) and APH1 (APH1aL, APH1aS, or APH1b). Whether the composition of a given γ-secretase complex determines a specific cellular targeting remains unsolved. Here we combined a bidirectional inducible promoter and 2A peptide technology to generate constructs for the temporary, stoichiometric co-expression of six different combinations of the four γ-secretase subunits including EGFP-tagged nicastrin. These plasmids allow for the formation of functional γ-secretase complexes displaying specific activities and maturations. We show that PS1-containing γ-secretase complexes were targeted to the plasma membrane, whereas PS2-containing ones were addressed to the trans-Golgi network, to recycling endosomes, and, depending on the APH1-variant, to late endocytic compartments. Overall, these novel constructs unravel a presenilin-dependent subcellular targeting of γ-secretase complexes. These tools should prove useful to determine whether the cellular distribution of γ-secretase complexes contributes to substrate selectivity and to delineate regulations of their trafficking.
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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.