ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Novel GαS-protein signaling associated with membrane-tethered amyloid precursor protein intracellular domain.
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 34 papers.
What it found
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Trial
- Therapeutic and preventive strategies based on the maladaptive plasticity hypothesis for Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Article
- Human microRNA (miR-20b-5p) modulates Alzheimer's disease pathways and neuronal function, and a specific polymorphism close to the MIR20B gene influences Alzheimer's biomarkers.Molecular psychiatry · 2022Article
- Excessive/Aberrant and Maladaptive Synaptic Plasticity: A Hypothesis for the Pathogenesis of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-β oligomerizes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- New Insights Into Blood-Brain Barrier Maintenance: The Homeostatic Role of β-Amyloid Precursor Protein in Cerebral Vasculature.Frontiers in physiology · 2020Review
- A pleiotropic role for exosomes loaded with the amyloid β precursor protein carboxyl-terminal fragments in the brain of Down syndrome patients.Neurobiology of aging · 2019Article
- APP-Mediated Signaling Prevents Memory Decline in Alzheimer's Disease Mouse Model.Cell reports · 2019Article
- Exosome Production Is Key to Neuronal Endosomal Pathway Integrity in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Inactivation of γ-secretases leads to accumulation of substrates and non-Alzheimer neurodegeneration.EMBO molecular medicine · 2017Article
- Not just amyloid: physiological functions of the amyloid precursor protein family.Nature reviews. Neuroscience · 2017Review
- The Role of APP in Structural Spine Plasticity.Frontiers in molecular neuroscience · 2017Review
- Role of APP Interactions with Heterotrimeric G Proteins: Physiological Functions and Pathological Consequences.Frontiers in molecular neuroscience · 2017Review
- Amyloid Precursor Protein family as unconventional Go-coupled receptors and the control of neuronal motility.Neurogenesis (Austin, Tex.) · 2017Review
- Exosomes in the Diseased Brain: First Insights fromFrontiers in neuroscience · 2017Review
- ZDHHC3 Tyrosine Phosphorylation Regulates Neural Cell Adhesion Molecule Palmitoylation.Molecular and cellular biology · 2016Article
- Article
- APP Receptor? To Be or Not To Be.Trends in pharmacological sciences · 2016Review
- The APP Intracellular Domain Is Required for Normal Synaptic Morphology, Synaptic Plasticity, and Hippocampus-Dependent Behavior.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Numerous physiological functions, including a role as a cell surface receptor, have been ascribed to Alzheimer's disease-associated amyloid precursor protein (APP). However, detailed analysis of intracellular signaling mediated by APP in neurons has been lacking. Here, we characterized intrinsic signaling associated with membrane-bound APP C-terminal fragments, which are generated following APP ectodomain release by α- or β-secretase cleavage. We found that accumulation of APP C-terminal fragments or expression of membrane-tethered APP intracellular domain results in adenylate cyclase-dependent activation of PKA (protein kinase A) and inhibition of GSK3β signaling cascades, and enhancement of axodendritic arborization in rat immortalized hippocampal neurons, mouse primary cortical neurons, and mouse neuroblastoma. We discovered an interaction between BBXXB motif of APP intracellular domain and the heterotrimeric G-protein subunit Gα(S), and demonstrate that Gα(S) coupling to adenylate cyclase mediates membrane-tethered APP intracellular domain-induced neurite outgrowth. Our study provides clear evidence that APP intracellular domain can have a nontranscriptional role in regulating neurite outgrowth through its membrane association. The novel functional coupling of membrane-bound APP C-terminal fragments with Gα(S) signaling identified in this study could impact several brain functions such as synaptic plasticity and memory formation.
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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.