ArticleThe Journal of biological chemistry2014
Sequential delivery of synaptic GluA1- and GluA4-containing AMPA receptors (AMPARs) by SAP97 anchored protein complexes in classical conditioning.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Metabotropic Glutamate Receptor-Dependent Synaptic Plasticity in Age-Related Neurodegenerative Disorders.Neural plasticity · 2026Review
- Restoration of nNOS Expression Rescues Autistic-Like Phenotypes Through Normalization of AMPA Receptor-Mediated Neurotransmission.Molecular neurobiology · 2024Article
- Polarized transport requires AP-1-mediated recruitment of KIF13A and KIF13B at the trans-Golgi.Molecular biology of the cell · 2024Article
- Synaptic Mechanisms of Delay Eyeblink Classical Conditioning: AMPAR Trafficking and Gene Regulation in an In Vitro Model.Molecular neurobiology · 2023Review
- Anxiolytic reversal of classically conditioned / chronic stress-induced gene expression and learning in the Stress Alternatives Model.Behavioural brain research · 2023Article
- AMPA receptors and their minions: auxiliary proteins in AMPA receptor trafficking.Cellular and molecular life sciences : CMLS · 2019Review
- Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines.Developmental neurobiology · 2017Article
- Subunit-specific synaptic delivery of AMPA receptors by auxiliary chaperone proteins TARPγ8 and GSG1L in classical conditioning.Neuroscience letters · 2017Article
- Primetime for Learning Genes.Genes · 2017Review
- Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A Critical Role for the GluA1 Accessory Protein, SAP97, in Cocaine Seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Coincidence detection in a neural correlate of classical conditioning is initiated by bidirectional 3-phosphoinositide-dependent kinase-1 signalling and modulated by adenosine receptors.The Journal of physiology · 2015Article
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Authors and funding
2 authors at 1 institution in 1 country.
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Abstract
Multiple signaling pathways are involved in AMPAR trafficking to synapses during synaptic plasticity and learning. The mechanisms for how these pathways are coordinated in parallel but maintain their functional specificity involves subcellular compartmentalization of kinase function by scaffolding proteins, but how this is accomplished is not well understood. Here, we focused on characterizing the molecular machinery that functions in the sequential synaptic delivery of GluA1- and GluA4-containing AMPARs using an in vitro model of eyeblink classical conditioning. We show that conditioning induces the interaction of selective protein complexes with the key structural protein SAP97, which tightly regulates the synaptic delivery of GluA1 and GluA4 AMPAR subunits. The results demonstrate that in the early stages of conditioning the initial activation of PKA stimulates the formation of a SAP97-AKAP/PKA-GluA1 protein complex leading to synaptic delivery of GluA1-containing AMPARs through a SAP97-PSD95 interaction. This is followed shortly thereafter by generation of a SAP97-KSR1/PKC-GluA4 complex for GluA4 AMPAR subunit delivery again through a SAP97-PSD95 interaction. These data suggest that SAP97 forms the molecular backbone of a protein scaffold critical for delivery of AMPARs to the PSD during conditioning. Together, the findings reveal a cooperative interaction of multiple scaffolding proteins for appropriately timed delivery of subunit-specific AMPARs to synapses and support a sequential two-stage model of AMPAR synaptic delivery during classical conditioning.
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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.