ArticleJournal of molecular neuroscience : MN2007
Tyr687 dependent APP endocytosis and Abeta production.
Article in Journal of molecular neuroscience : MN, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Protein Phosphorylation Alterations in Myotonic Dystrophy Type 1: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Aβ Modulates Extracellular Vesicles Proteomic Profile Impacting Phosphorylation Mediators.Molecular neurobiology · 2025Article
- Spectroscopic Profile of Metabolome Dynamics During Rat Cortical Neuronal Differentiation.International journal of molecular sciences · 2025Article
- Phosphoproteome Microarray Analysis of Extracellular Particles as a Tool to Explore Novel Biomarker Candidates for Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Cooperative effects of SIRT1 and SIRT2 on APP acetylation.Aging cell · 2023Article
- Gamma frequency light flicker regulates amyloid precursor protein trafficking for reducing β-amyloid load in Alzheimer's disease model.Aging cell · 2022Article
- A Bioinformatics Approach Toward Unravelling the Synaptic Molecular Crosstalk Between Alzheimer's Disease and Diabetes.Journal of Alzheimer's disease : JAD · 2022Article
- The role of the integral type II transmembrane protein BRI2 in health and disease.Cellular and molecular life sciences : CMLS · 2021Review
- TrkB receptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer's disease pathologies.Molecular psychiatry · 2021Article
- Metabolic Alterations in Myotonic Dystrophy Type 1 and Their Correlation with Lipin.International journal of environmental research and public health · 2021Review
- Glymphatic system, AQP4, and their implications in Alzheimer's disease.Neurological research and practice · 2021Review
- The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Phosphorylation Signaling in APP Processing in Alzheimer's Disease.International journal of molecular sciences · 2019Review
- Aβ Influences Cytoskeletal Signaling Cascades with Consequences to Alzheimer's Disease.Molecular neurobiology · 2015Review
- Golgi defects enhance APP amyloidogenic processing in Alzheimer's disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2015Review
- LAP1 is a crucial protein for the maintenance of the nuclear envelope structure and cell cycle progression.Molecular and cellular biochemistry · 2015Article
- Article
- Protein kinase C and rho activated coiled coil protein kinase 2 (ROCK2) modulate Alzheimer's APP metabolism and phosphorylation of the Vps10-domain protein, SorL1.Molecular neurodegeneration · 2010Article
- Retrieval of the Alzheimer's amyloid precursor protein from the endosome to the TGN is S655 phosphorylation state-dependent and retromer-mediated.Molecular neurodegeneration · 2010Article
- Induced dimerization of the amyloid precursor protein leads to decreased amyloid-beta protein production.The Journal of biological chemistry · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neurotoxic Abeta peptide is derived by proteolytic processing from the Alzheimer's amyloid precursor protein (APP), whose short cytoplasmic domain contains several phosphorylatable amino acids. The latter can be phosphorylated 'in vitro' and 'in vivo,' and in some cases phosphorylation appears to be associated with the disease condition. Using APP-GFP fusion proteins to monitor APP processing, the role of Tyr687 was addressed by mimicking its constitutive phosphorylation (Y687E) and dephosphorylation (Y687F). Contrasting effects on subcellular APP distribution were observed. Y687E-APP-GFP was targeted to the membrane but could not be detected in transferrin containing vesicular structures, and exhibited a concomitant and dramatic decrease in Abeta production. In contrast, Y687F-APP-GFP was endocytosed similarly to wild type APP, but was relatively favoured for beta-secretase cleavage. Overall, Tyr687 appears to be a critical residue determining APP targeting and processing via different pathways, including endocytosis and retrograde transport. Significantly, from a disease perspective, mimicking Tyr687 phosphorylation resulted in a hitherto undescribed inhibition of Abeta production. Our results provide novel insights into the role of direct APP phosphorylation on APP targeting, processing and Abeta production.
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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.