ArticleProceedings of the National Academy of Sciences of the United States of America2015
Regulation of AMPA receptor subunit GluA1 surface expression by PAK3 phosphorylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- PACSIN2-mediated synaptic injury contributes to behavioral disorders caused by chronic stress.Acta pharmacologica Sinica · 2026Article
- PAK1 (p21-Activated Kinase 1) and Its Role in Neurodevelopmental Disorders-New Case Report and a Comprehensive Review.International journal of molecular sciences · 2025Review
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- The Role of ΔFosB in the Pathogenesis of Levodopa-Induced Dyskinesia: Mechanisms and Therapeutic Strategies.Molecular neurobiology · 2025Review
- Aging activates escape of the silent X chromosome in the female mouse hippocampus.Science advances · 2025Article
- Synaptic Plasticity Linked to Ionotropic Glutamate Receptors After Nicotine Exposure.Current neuropharmacology · 2025Review
- Dancing Glycoproteins: Memory Pattern Formation by Protein Folding through Hydrogen Bonding.Current medicinal chemistry · 2025Article
- EphB2 Signaling Is Implicated in Astrocyte-Mediated Parvalbumin Inhibitory Synapse Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Phosphorylation of Doc2 by EphB2 modulates Munc13-mediated SNARE complex assembly and neurotransmitter release.Science advances · 2024Article
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- The molecular basis of p21-activated kinase-associated neurodevelopmental disorders: From genotype to phenotype.Frontiers in neuroscience · 2023Review
- Activity-Induced Cortical Glutamatergic Neuron Nascent Proteins.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Tau target identification reveals NSF-dependent effects on AMPA receptor trafficking and memory formation.The EMBO journal · 2022Article
- Phosphoproteomic of the acetylcholine pathway enables discovery of the PKC-β-PIX-Rac1-PAK cascade as a stimulatory signal for aversive learning.Molecular psychiatry · 2022Article
- Understanding the physical basis of memory: Molecular mechanisms of the engram.The Journal of biological chemistry · 2022Review
- Sex and chronic stress alter the distribution of glutamate receptors within rat hippocampal CA3 pyramidal cells following oxycodone conditioned place preference.Neurobiology of stress · 2022Article
- Angiotensin II Infusion Results in Both Hypertension and Increased AMPA GluA1 Signaling in Hypothalamic Paraventricular Nucleus of Male but not Female Mice.Neuroscience · 2022Article
- The p21-activated kinases in neural cytoskeletal remodeling and related neurological disorders.Protein & cell · 2022Review
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
AMPA receptors (AMPARs) are the major excitatory receptors of the brain and are fundamental to synaptic plasticity, memory, and cognition. Dynamic recycling of AMPARs in neurons is regulated through several types of posttranslational modification, including phosphorylation. Here, we identify a previously unidentified signal transduction cascade that modulates phosphorylation of serine residue 863 (S863) in the GluA1 AMPAR subunit and controls surface trafficking of GluA1 in neurons. Activation of the EphR-Ephrin signal transduction pathway enhances S863 phosphorylation. Further, EphB2 can interact with Zizimin1, a guanine-nucleotide exchange factor that activates Cdc42 and stimulates S863 phosphorylation in neurons. Among the numerous targets downstream of Cdc42, we determined that the p21-activated kinase-3 (PAK3) phosphorylates S863 in vitro. Moreover, specific loss of PAK3 expression and pharmacological inhibition of PAK both disrupt activity-dependent phosphorylation of S863 in cortical neurons. EphB2, Cdc42, and PAKs are broadly capable of controlling dendritic spine formation and synaptic plasticity and are implicated in multiple cognitive disorders. Collectively, these data delineate a novel signal cascade regulating AMPAR trafficking that may contribute to the molecular mechanisms that govern learning and cognition.
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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.