ArticleProceedings of the National Academy of Sciences of the United States of America2011
ADP ribosylation factor 6 (ARF6) controls amyloid precursor protein (APP) processing by mediating the endosomal sorting of BACE1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers, 2 of them syntheses that pooled it.
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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
150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 242 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Pooled it
- The exocyst is an insulin-sensitive regulator of amyloid precursor protein trafficking and amyloid-beta generation in neurons.bioRxiv : the preprint server for biology · 2026Article
- ISX9 activates the Wnt/β-catenin signaling pathway and exerts neuroprotective effects in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Amyloid Beta Oligomers as Early Triggers of Neuronal Cytoskeleton Dysfunction in Alzheimer's Disease.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Endothelial Arf6 sustains capillary electrical signaling and cerebral blood flow through PIPbioRxiv : the preprint server for biology · 2025Article
- Beyond Clathrin: Decoding the Mechanism of Ultrafast Endocytosis.Physiology (Bethesda, Md.) · 2025Review
- EFA6A, a Guanine Nucleotide Exchange Factor for Arf6, Regulates Developmental Stage-Dependent Spine Morphogenesis, Synaptic Plasticity, and Long-Term Memory in the Hippocampus.Molecular neurobiology · 2025Article
- The calcium pump PMCA4b promotes epithelial cell polarization and lumen formation.Communications biology · 2025Article
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.The Biochemical journal · 2024Review
- Kismet/CHD7/CHD8 and Amyloid Precursor Protein-like Regulate Synaptic Levels of Rab11 at theInternational journal of molecular sciences · 2024Article
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Investigation of Potential Drug Targets Involved in Inflammation Contributing to Alzheimer's Disease Progression.Pharmaceuticals (Basel, Switzerland) · 2024Review
- BIN1 in the Pursuit of Ousting the Alzheimer's Reign: Impact on Amyloid and Tau Neuropathology.Neurotoxicity research · 2023Review
- Amyloid Precursor Protein and Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Amyloid fibril proteomics of AD brains reveals modifiers of aggregation and toxicity.Molecular neurodegeneration · 2023Article
- Evidence for a clathrin-independent endocytic pathway for APP internalization in the neuronal somatodendritic compartment.Cell reports · 2023Article
- Review
- 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
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyloid β (Aβ) peptides, the primary constituents of senile plaques and a hallmark in Alzheimer's disease pathology, are generated through the sequential cleavage of amyloid precursor protein (APP) by β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. The early endosome is thought to represent a major compartment for APP processing; however, the mechanisms of how BACE1 encounters APP are largely unknown. In contrast to APP internalization, which is clathrin-dependent, we demonstrate that BACE1 is sorted to early endosomes via a route controlled by the small GTPase ADP ribosylation factor 6 (ARF6). Altering ARF6 levels or its activity affects endosomal sorting of BACE1, and consequently results in altered APP processing and Aβ production. Furthermore, sorting of newly internalized BACE1 from ARF6-positive towards RAB GTPase 5 (RAB5)-positive early endosomes depends on its carboxyterminal short acidic cluster-dileucine motif. This ARF6-mediated sorting of BACE1 is confined to the somatodendritic compartment of polarized neurons in agreement with Aβ peptides being primarily secreted from here. These results demonstrate a spatial separation between APP and BACE1 during surface-to-endosome transport, suggesting subcellular trafficking as a regulatory mechanism for this proteolytic processing step. It thereby provides a novel avenue to interfere with Aβ production through a selective modulation of the distinct endosomal transport routes used by BACE1 or APP.
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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.