ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Flotillin-dependent clustering of the amyloid precursor protein regulates its endocytosis and amyloidogenic processing in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 201 citations in OpenAlex.
- Synaptobrevin-2 Containing Extracellular Vesicles Are Rapidly Incorporated Into Mammalian Neurons via a Dynamin-Dependent Pathway.Journal of neurochemistry · 2026Article
- Clustering hinders APP α-secretase processing in the plasma membrane.Biophysical journal · 2026Article
- Molecular mechanisms of flotillin complexes in organizing membrane microdomains.Nature communications · 2026Article
- Role of Flotillin-1 In Listeria monocytogenes Cell-to-Cell Spreading.The Journal of infectious diseases · 2025Article
- Beyond Clathrin: Decoding the Mechanism of Ultrafast Endocytosis.Physiology (Bethesda, Md.) · 2025Review
- Cell-specific copper dyshomeostasis mechanism in Alzheimer's disease.Translational neurodegeneration · 2025Review
- Revisiting Pathogen Exploitation of Clathrin-Independent Endocytosis: Mechanisms and Implications.Cells · 2025Review
- Flotillins in membrane trafficking and physiopathology.Biology of the cell · 2025Review
- Flotillins affect LPS-induced TLR4 signaling by modulating the trafficking and abundance of CD14.Cellular and molecular life sciences : CMLS · 2024Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Cholesterol modulation of interactions between psychostimulants and dopamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment.Cell reports · 2023Article
- AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.Traffic (Copenhagen, Denmark) · 2023Article
- Upregulation of endocytic protein expression in the Alzheimer's disease male human brain.Aging brain · 2023Article
- Insight into the role of clathrin-mediated endocytosis inhibitors in SARS-CoV-2 infection.Reviews in medical virology · 2023Review
- Loss of endosomal exchanger NHE6 leads to pathological changes in tau in human neurons.Stem cell reports · 2022Article
- Modeling the early stages of Alzheimer's disease by administering intracerebroventricular injections of human native Aβ oligomers to rats.Acta neuropathologica communications · 2022Article
- Effect of Sublethal Copper Overload on CholesterolACS omega · 2022Article
53 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The flotillins/reggie proteins are associated with noncaveolar membrane microdomains and have been implicated in the regulation of a clathrin- and caveolin-independent endocytosis pathway. Endocytosis is required for the amyloidogenic processing of the amyloid precursor protein (APP) and thus to initiate the release of the neurotoxic beta-amyloid peptide (Abeta), the major component of extracellular plaques found in the brains of Alzheimer's disease patients. Here, we report that small interference RNA-mediated downregulation of flotillin-2 impairs the endocytosis of APP, in both neuroblastoma cells and primary cultures of hippocampal neurons, and reduces the production of Abeta. Similar to tetanus neurotoxin endocytosis, but unlike the internalization of transferrin, clathrin-dependent endocytosis of APP requires cholesterol and adaptor protein-2 but is independent of epsin1 function. Moreover, on a nanoscale resolution using stimulated emission depletion microscopy and by Förster resonance energy transfer with fluorescence lifetime imaging microscopy, we provide evidence that flotillin-2 promotes the clustering of APP at the cell surface. We show that the interaction of flotillin-2 with APP is dependent on cholesterol and that clustering of APP enhances its endocytosis rate. Together, our data suggest that cholesterol/flotillin-dependent clustering of APP may stimulate the internalization into a specialized clathrin-dependent endocytosis pathway to promote amyloidogenic processing.
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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.