ArticlePloS one2016
Tyrosine Binding Protein Sites Regulate the Intracellular Trafficking and Processing of Amyloid Precursor Protein through a Novel Lysosome-Directed Pathway.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- 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
- Lysosomal dysfunction in Down syndrome and Alzheimer mouse models is caused by v-ATPase inhibition by TyrScience advances · 2023Article
- HIV-1 promotes ubiquitination of the amyloidogenic C-terminal fragment of APP to support viral replication.Nature communications · 2023Article
- Endosomal trafficking and related genetic underpinnings as a hub in Alzheimer's disease.Journal of cellular physiology · 2022Review
- Amyloid Beta Is InternalizedFrontiers in molecular neuroscience · 2022Article
- Endosomal-lysosomal dysfunctions in Alzheimer's disease: Pathogenesis and therapeutic interventions.Metabolic brain disease · 2021Review
- Motifs and interface amino acid-mediated regulation of amyloid biogenesis in microbes to humans: potential targets for intervention.Biophysical reviews · 2020Review
- Microglia in Alzheimer's Disease: Exploring How Genetics and Phenotype Influence Risk.Journal of molecular biology · 2019Review
- Cellular Trafficking of Amyloid Precursor Protein in Amyloidogenesis Physiological and Pathological Significance.Molecular neurobiology · 2019Review
- 27-Hydroxycholesterol Contributes to Lysosomal Membrane Permeabilization-Mediated Pyroptosis in Co-cultured SH-SY5Y Cells and C6 Cells.Frontiers in molecular neuroscience · 2019Article
- Contribution of the Endosomal-Lysosomal and Proteasomal Systems in Amyloid-β Precursor Protein Derived Fragments Processing.Frontiers in cellular neuroscience · 2018Article
- Possible Clues for Brain Energy Translation via Endolysosomal Trafficking of APP-CTFs in Alzheimer's Disease.Oxidative medicine and cellular longevity · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The amyloid hypothesis posits that the production of β-amyloid (Aβ) aggregates leads to neurodegeneration and cognitive decline associated with AD. Aβ is produced by sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretase. While nascent APP is well known to transit to the endosomal/ lysosomal system via the cell surface, we have recently shown that APP can also traffic to lysosomes intracellularly via its interaction with AP-3. Because AP-3 interacts with cargo protein via interaction with tyrosine motifs, we mutated the three tyrosines motif in the cytoplasmic tail of APP. Here, we show that the YTSI motif interacts with AP-3, and phosphorylation of the serine in this motif disrupts the interaction and decreases APP trafficking to lysosomes. Furthermore, we show that phosphorylation at this motif can decrease the production of neurotoxic Aβ 42. This demonstrates that reducing APP trafficking to lysosomes may be a strategy to reduce Aβ 42 in Alzheimer's disease.
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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.