ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Adaptor protein APPL1 couples synaptic NMDA receptor with neuronal prosurvival phosphatidylinositol 3-kinase/Akt pathway.
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 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
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- Excitatory Synaptic Transmission in Ischemic Stroke: A New Outlet for Classical Neuroprotective Strategies.International journal of molecular sciences · 2022Review
- Central Adiponectin Signaling - A Metabolic Regulator in Support of Brain Plasticity.Brain plasticity (Amsterdam, Netherlands) · 2022Review
- Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins.Cells · 2021Review
- Adaptor protein APPL1 links neuronal activity to chromatin remodeling in cultured hippocampal neurons.Journal of molecular cell biology · 2021Article
- Superoxide and Non-ionotropic Signaling in Neuronal Excitotoxicity.Frontiers in neuroscience · 2020Review
- NMDA receptor modulation of glutamate release in activated neutrophils.EBioMedicine · 2019Article
- Variation within voltage-gated calcium channel genes and antipsychotic treatment response in a South African first episode schizophrenia cohort.The pharmacogenomics journal · 2019Article
- Excitotoxic superoxide production and neuronal death require both ionotropic and non-ionotropic NMDA receptor signaling.Scientific reports · 2018Article
- EphrinB/EphB forward signaling in Müller cells causes apoptosis of retinal ganglion cells by increasing tumor necrosis factor alpha production in rat experimental glaucomatous model.Acta neuropathologica communications · 2018Article
- Reduced synaptic function of Kainate receptors in the insular cortex of Fmr1 Knock-out mice.Molecular brain · 2018Article
- Chaperone-E3 Ligase Complex HSP70-CHIP Mediates Ubiquitination of Ribosomal Protein S3.International journal of molecular sciences · 2018Article
- De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.Brain : a journal of neurology · 2018Article
- Mechanistic target of rapamycin complex 1 and 2 in human temporal lobe epilepsy.Annals of neurology · 2018Article
- Endocytic Adaptor Protein HIP1R Controls Intracellular Trafficking of Epidermal Growth Factor Receptor in Neuronal Dendritic Development.Frontiers in molecular neuroscience · 2018Article
- Intranasal administration of recombinant Netrin-1 attenuates neuronal apoptosis by activating DCC/APPL-1/AKT signaling pathway after subarachnoid hemorrhage in rats.Neuropharmacology · 2017Article
- APPL1 prevents pancreatic beta cell death and inflammation by dampening NFκB activation in a mouse model of type 1 diabetes.Diabetologia · 2017Article
- Huntingtin-Interacting Protein 1-Related Protein Plays a Critical Role in Dendritic Development and Excitatory Synapse Formation in Hippocampal Neurons.Frontiers in molecular neuroscience · 2017Article
- Serine 707 of APPL1 is Critical for the Synaptic NMDA Receptor-Mediated Akt Phosphorylation Signaling Pathway.Neuroscience bulletin · 2016Article
- APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.The Journal of cell biology · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well known that NMDA receptors (NMDARs) can both induce neurotoxicity and promote neuronal survival under different circumstances. Recent studies show that such paradoxical responses are related to the receptor location: the former to the extrasynaptic and the latter to the synaptic. The phosphoinositide 3-kinase (PI3K)/Akt kinase cascade is a key pathway responsible for the synaptic NMDAR-dependent neuroprotection. However, it is still unknown how synaptic NMDARs are coupled with the PI3K/Akt pathway. Here, we explored the role of an adaptor protein-adaptor protein containing pH domain, PTB domain, and leucine zipper motif (APPL1)-in this signal coupling using rat cortical neurons. We found that APPL1 existed in postsynaptic densities and associated with the NMDAR complex through binding to PSD95 at its C-terminal PDZ-binding motif. NMDARs, APPL1, and the PI3K/Akt cascade formed a complex in rat cortical neurons. Synaptic NMDAR activity increased the association of this complex, induced activation of the PI3K/Akt pathway, and consequently protected neurons against starvation-induced apoptosis. Perturbing APPL1 interaction with PSD95 by a peptide comprising the APPL1 C-terminal PDZ-binding motif dissociated the PI3K/Akt pathway from NMDARs. Either the peptide or lentiviral knockdown of APPL1 blocked synaptic NMDAR-dependent recruitment and activation of PI3K/Akt pathway, and consequently blocked synaptic NMDAR-dependent neuroprotection. These results suggest that APPL1 contributes to connecting synaptic NMDARs with the intracellular PI3K/Akt cascade and the downstream prosurvival signaling pathway in rat cortical neurons.
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