ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Amyloid precursor protein dimerization and synaptogenic function depend on copper binding to the growth factor-like domain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 124 citations in OpenAlex.
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- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
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- The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer's disease.Open biology · 2024Article
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Current Insights of Nanocarrier-Mediated Gene Therapeutics to Treat Potential Impairment of Amyloid Beta Protein and Tau Protein in Alzheimer's Disease.Molecular neurobiology · 2024Review
- Amyloid, Crohn's disease, and Alzheimer's disease - are they linked?Frontiers in cellular and infection microbiology · 2024Review
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- Amyloid precursor protein and its interacting proteins in neurodevelopment.Biochemical Society transactions · 2023Review
- APP family member dimeric complexes are formed predominantly in synaptic compartments.Cell & bioscience · 2023Article
- The Reticulon-4 3-bp Deletion/Insertion Polymorphism Is Associated with Structural mRNA Changes and the Risk of Breast Cancer: A Population-Based Case-Control Study with Bioinformatics Analysis.Life (Basel, Switzerland) · 2023Article
- Differential effects of familial Alzheimer's disease-causing mutations on amyloid precursor protein (APP) trafficking, proteolytic conversion, and synaptogenic activity.Acta neuropathologica communications · 2023Article
- A Multilevel Study of Eupatorin and Scutellarein as Anti-Amyloid Agents in Alzheimer's Disease.Biomedicines · 2023Article
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- The Labyrinthine Landscape of APP Processing: State of the Art and Possible Novel Soluble APP-Related Molecular Players in Traumatic Brain Injury and Neurodegeneration.International journal of molecular sciences · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- A guide to selecting high-performing antibodies for amyloid-beta precursor protein for use in Western Blot, immunoprecipitation and immunofluorescence.F1000Research · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that the copper-binding amyloid precursor protein (APP) has an essential synaptic function. APP synaptogenic function depends on trans-directed dimerization of the extracellular E1 domain encompassing a growth factor-like domain (GFLD) and a copper-binding domain (CuBD). Here we report the 1.75 Å crystal structure of the GFLD in complex with a copper ion bound with high affinity to an extended hairpin loop at the dimerization interface. In coimmunoprecipitation assays copper binding promotes APP interaction, whereas mutations in the copper-binding sites of either the GFLD or CuBD result in a drastic reduction in APP cis-orientated dimerization. We show that copper is essential and sufficient to induce trans-directed dimerization of purified APP. Furthermore, a mixed culture assay of primary neurons with HEK293 cells expressing different APP mutants revealed that APP potently promotes synaptogenesis depending on copper binding to the GFLD. Together, these findings demonstrate that copper binding to the GFLD of APP is required for APP cis-/trans-directed dimerization and APP synaptogenic function. Thus, neuronal activity or disease-associated changes in copper homeostasis likely go along with altered APP synaptic function.
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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.