ArticleBMC cell biology2005
Inhibition of dynamin-dependent endocytosis increases shedding of the amyloid precursor protein ectodomain and reduces generation of amyloid beta protein.
Article in BMC cell biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 129 citations in OpenAlex.
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Review
- Clustering hinders APP α-secretase processing in the plasma membrane.Biophysical journal · 2026Article
- Endocytic Pathways Unveil the Role of Syndecans in the Seeding and Spreading of Pathological Protein Aggregates: Insights into Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- APP-BACE1 Interaction and Intracellular Localization Regulate Aβ Production in iPSC-Derived Cortical Neurons.Cellular and molecular neurobiology · 2023Article
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2023Article
- AP2S1 regulates APP degradation through late endosome-lysosome fusion in cells and APP/PS1 mice.Traffic (Copenhagen, Denmark) · 2023Article
- Enhanced cleavage of APP by co-expressed Bace1 alters the distribution of APP and its fragments in neuronal and non-neuronal cells.Molecular neurobiology · 2022Article
- Rab35 and glucocorticoids regulate APP and BACE1 trafficking to modulate Aβ production.Cell death & disease · 2021Article
- Endocytosis-pathway polygenic scores affects the hippocampal network connectivity and individualized identification across the high-risk of Alzheimer's disease.Brain imaging and behavior · 2021Article
- Inactive variants of death receptor p75The EMBO journal · 2021Article
- KCTD1 mutants in scalp‑ear‑nipple syndrome and AP‑2α P59A in Char syndrome reciprocally abrogate their interactions, but can regulate Wnt/β‑catenin signaling.Molecular medicine reports · 2020Article
- Inhibitory effects of curcumin on HMolecular biology reports · 2020Article
- Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons.Scientific reports · 2019Article
- Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein.Biomolecules & therapeutics · 2019Article
- Alzheimer Aβ Assemblies Accumulate in Excitatory Neurons upon Proteasome Inhibition and Kill Nearby NAKα3 Neurons by Secretion.iScience · 2019Article
- Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.The EMBO journal · 2018Review
- Overexpression of SNX3 Decreases Amyloid-β Peptide Production by Reducing Internalization of Amyloid Precursor Protein.Neuro-degenerative diseases · 2018Article
- Deficient Wnt Signaling and Synaptic Vulnerability in Alzheimer's Disease: Emerging Roles for the LRP6 Receptor.Frontiers in synaptic neuroscience · 2018Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe amyloid precursor protein (APP) is transported via the secretory pathway to the cell surface, where it may be cleaved within its ectodomain by alpha-secretase, or internalized within clathrin-coated vesicles. An alternative proteolytic pathway occurs within the endocytic compartment, where the sequential action of beta- and gamma-secretases generates the amyloid beta protein (Abeta). In this study, we investigated the effects of modulators of endocytosis on APP processing.
resultsHuman embryonic kidney cells were transfected with a dominant negative mutant of dynamin I, an important mediator of clathrin-dependent endocytosis, and APP proteolysis was analyzed. Overexpression of the mutant dynamin (dyn I K44A) resulted in increased shedding of the APP ectodomain (sAPPalpha), accumulation of the C-terminal alpha-secretase product C83, and a reduction in the release of Abeta. Levels of mature APP on the cell surface were increased in cells expressing dyn I K44A, and internalization of surface-immunolabeled APP, assessed by fluorescence microscopy, was inhibited. Dynamin is a substrate for protein kinase C (PKC), and it was hypothesized that activators of PKC, which are known to stimulate alpha-secretase-mediated cleavage of APP, might exert their effects by inhibiting dynamin-dependent endocytosis. However, the internalization of surface-biotinylated APP was unaffected by treatment of cells with phorbol 12-myristate 13-acetate in the presence of the alpha-secretase inhibitor TAPI-1.
conclusionThe results indicate that APP is internalized by a dynamin-dependent process, and suggest that alterations in the activity of proteins that mediate endocytosis might lead to significant changes in Abeta production.
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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.