ArticleeLife2020
Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 31 citations in OpenAlex.
- SANS reveals lipid-dependent oligomerization of an intramembrane aspartyl protease from H. volcanii.Biophysical journal · 2024Article
- Celebrating the Birthday of AMPA Receptor Nanodomains: Illuminating the Nanoscale Organization of Excitatory Synapses with 10 Nanocandles.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Review
- Advancements and Practical Considerations for Biophysical Research: Navigating the Challenges and Future of Super-resolution Microscopy.Chemical & biomedical imaging · 2024Review
- The functional role of Higd1a in mitochondrial homeostasis and in multiple disease processes.Genes & diseases · 2023Review
- Presenilins and mitochondria-an intriguing link: mini-review.Frontiers in neuroscience · 2023Review
- γ-Secretase in Alzheimer's disease.Experimental & molecular medicine · 2022Review
- 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
- Flying under the radar: CDH2 (N-cadherin), an important hub molecule in neurodevelopmental and neurodegenerative diseases.Frontiers in neuroscience · 2022Review
- Super-resolution microscopy: a closer look at synaptic dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2021Review
- Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains.Molecular brain · 2021Article
- Knock-in tagging in zebrafish facilitated by insertion into non-coding regions.Development (Cambridge, England) · 2021Article
- Assembly of γ-secretase occurs through stable dimers after exit from the endoplasmic reticulum.The Journal of cell biology · 2021Article
- Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Alteration in synaptic nanoscale organization dictates amyloidogenic processing in Alzheimer's disease.iScience · 2021Article
- Tissue Clearing and Expansion Methods for Imaging Brain Pathology in Neurodegeneration: From Circuits to Synapses and Beyond.Frontiers in neuroscience · 2020Review
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
γ-Secretase is a multi-subunit enzyme whose aberrant activity is associated with Alzheimer's disease and cancer. While its structure is atomically resolved, γ-secretase localization in the membrane in situ relies mostly on biochemical data. Here, we combined fluorescent tagging of γ-secretase subunits with super-resolution microscopy in fibroblasts. Structured illumination microscopy revealed single γ-secretase complexes with a monodisperse distribution and in a 1:1 stoichiometry of PSEN1 and nicastrin subunits. In living cells, sptPALM revealed PSEN1/γ-secretase mainly with directed motility and frequenting 'hotspots' or high track-density areas that are sensitive to γ-secretase inhibitors. We visualized γ-secretase association with substrates like amyloid precursor protein and N-cadherin, but not with its sheddases ADAM10 or BACE1 at the cell surface, arguing against pre-formed megadalton complexes. Nonetheless, in living cells PSEN1/γ-secretase transiently visits ADAM10 hotspots. Our results highlight the power of super-resolution microscopy for the study of γ-secretase distribution and dynamics in the membrane.
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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.