ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Intracellular amyloid precursor protein sorting and amyloid-β secretion are regulated by Src-mediated phosphorylation of Mint2.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- AP2A1 activates Rab7 to promote axonal autophagosome transport and slow the progression of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- 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
- A comprehensive bibliometric analysis of global research on the role of acrolein in Alzheimer's disease pathogenesis: involvement of amyloid-beta.Frontiers in aging neuroscience · 2024Article
- Interrogation and validation of the interactome of neuronal Munc18-interacting Mint proteins with AlphaFold2.The Journal of biological chemistry · 2024Article
- Tight control of the APP-Mint1 interaction in regulating amyloid production.Brain research · 2023Article
- Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease.Journal of cellular physiology · 2022Review
- Human APOER2 Isoforms Have Differential Cleavage Events and Synaptic Properties.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Dementia subtype prediction models constructed by penalized regression methods for multiclass classification using serum microRNA expression data.Scientific reports · 2021Article
- WIPER: Weighted in-Path Edge Ranking for biomolecular association networks.Quantitative biology (Beijing, China) · 2019Article
- Attenuation of amyloid-β generation by atypical protein kinase C-mediated phosphorylation of engulfment adaptor PTB domain containing 1 threonine 35.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Candidate-based screening via gene modulation in human neurons and astrocytes implicates FERMT2 in Aβ and TAU proteostasis.Human molecular genetics · 2019Article
- Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.Molecular neurobiology · 2019Review
- TheThe Journal of biological chemistry · 2019Article
- Alcohol drinking exacerbates neural and behavioral pathology in the 3xTg-AD mouse model of Alzheimer's disease.International review of neurobiology · 2019Review
- Measuring the Endocytic Recycling of Amyloid Precursor Protein (APP) in Neuro2a Cells.Bio-protocol · 2017Article
- Bin1 and CD2AP polarise the endocytic generation of beta-amyloid.EMBO reports · 2017Article
- BECN1/Beclin 1 sorts cell-surface APP/amyloid β precursor protein for lysosomal degradation.Autophagy · 2016Article
- Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein.Journal of neurochemistry · 2016Article
- APP Receptor? To Be or Not To Be.Trends in pharmacological sciences · 2016Review
- Amyloid-beta Alzheimer targets - protein processing, lipid rafts, and amyloid-beta pores.The Yale journal of biology and medicine · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mint adaptor proteins bind to the membrane-bound amyloid precursor protein (APP) and affect the production of pathogenic amyloid-β (Aβ) peptides related to Alzheimer's disease (AD). Previous studies have shown that loss of each of the three Mint proteins delays the age-dependent production of amyloid plaques in transgenic mouse models of AD. However, the cellular and molecular mechanisms underlying Mints effect on amyloid production are unclear. Because Aβ generation involves the internalization of membrane-bound APP via endosomes and Mints bind directly to the endocytic motif of APP, we proposed that Mints are involved in APP intracellular trafficking, which in turn, affects Aβ generation. Here, we show that APP endocytosis was attenuated in Mint knock-out neurons, revealing a role for Mints in APP trafficking. We also show that the endocytic APP sorting processes are regulated by Src-mediated phosphorylation of Mint2 and that internalized APP is differentially sorted between autophagic and recycling trafficking pathways. A Mint2 phosphomimetic mutant favored endocytosis of APP along the autophagic sorting pathway leading to increased intracellular Aβ accumulation. Conversely, the Mint2 phospho-resistant mutant increased APP localization to the recycling pathway and back to the cell surface thereby enhancing Aβ42 secretion. These results demonstrate that Src-mediated phosphorylation of Mint2 regulates the APP endocytic sorting pathway, providing a mechanism for regulating Aβ secretion.
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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.