ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Tuning of Glutamate, But Not GABA, Release by an Intrasynaptic Vesicle APP Domain Whose Function Can Be Modulated by β- or α-Secretase Cleavage.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Estradiol ameliorates AD pathology and cognitive deficits by SORLA-mediated APP endosomal trafficking.Alzheimer's research & therapy · 2026Article
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Article
- Regulation of gene expression by the APP family in the adult cerebral cortex.Scientific reports · 2022Article
- Late-long-term potentiation magnitude, but not Aβ levels and amyloid pathology, is associated with behavioral performance in a rat knock-in model of Alzheimer disease.Frontiers in aging neuroscience · 2022Article
- Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission.Scientific reports · 2021Article
- MicrogliaeLife · 2020Article
- Knock-in rats with homozygousThe Journal of biological chemistry · 2020Article
- Article
- Glutamate in Male and Female Sexual Behavior: Receptors, Transporters, and Steroid Independence.Frontiers in behavioral neuroscience · 2020Review
- GABAergic Inhibitory Interneuron Deficits in Alzheimer's Disease: Implications for Treatment.Frontiers in neuroscience · 2020Review
- Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock-in rats with increased β-cleavage of APP.Aging cell · 2019Article
- Danish and British dementia ITM2b/BRI2 mutations reduce BRI2 protein stability and impair glutamatergic synaptic transmission.The Journal of biological chemistryArticle
- TNF-α-mediated reduction in inhibitory neurotransmission precedes sporadic Alzheimer's disease pathology in young Trem2The Journal of biological chemistryArticle
- Is γ-secretase a beneficial inactivating enzyme of the toxic APP C-terminal fragment C99?The Journal of biological chemistryReview
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
APP, whose mutations cause familial Alzheimer's disease (FAD), modulates neurotransmission via interaction of its cytoplasmic tail with the synaptic release machinery. Here we identified an intravesicular domain of APP, called intraluminal SV-APP interacting domain (ISVAID), which interacts with glutamatergic, but not GABAergic, synaptic vesicle proteins. ISVAID contains the β- and α-secretase cleavage sites of APP: proteomic analysis of the interactome of ISVAID suggests that β- and α-secretase cleavage of APP cuts inside the interaction domain of ISVAID and destabilizes protein-protein interactions. We have tested the functional significance of the ISVAID and of β-/α-secretase-processing of APP using various ISVAID-derived peptides in competition experiments on both female and male mouse and rats hippocampal slices. A peptide encompassing the entire ISVAID facilitated glutamate, but not GABA, release acting as dominant negative inhibitor of the functions of this APP domain in acute hippocampal slices. In contrast, peptides representing the product of β-/α-secretase-processing of ISVAID did not alter excitatory neurotransmitter release. These findings suggest that cleavage of APP by either β- or α-secretase may inactivate the ISVAID, thereby enhancing glutamate release. Our present data support the notion that APP tunes glutamate release, likely through intravesicular and extravesicular interactions with synaptic vesicle proteins and the neurotransmitter release machinery, and that β-/α cleavage of APP facilitates the release of excitatory neurotransmitter.
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