Cited by 170Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingSignaling Pathways in Disease

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Regulation of A-kinase anchoring protein 79/150-cAMP-dependent protein kinase postsynaptic targeting by NMDA receptor activation of calcineurin and remodeling of dendritic actin

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Gomez, Lisa. L., Alam, Shuvo, Smith, Karen E., Horne, Eric, Dell'Acqua, Mark L.·2002·The Journal of Neuroscience

DOI 10.1523/jneurosci.22-16-07027.2002PMC PMC6757891

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Abstract

At the postsynaptic membrane of glutamatergic synapses, the cAMP-dependent protein kinase (PKA), protein kinase C (PKC), and calcineurin (CaN) anchoring protein AKAP79/150 is recruited to NMDA and AMPA glutamate receptors by postsynaptic density (PSD)-95 family membrane-associated guanylate kinase (MAGUK) scaffold proteins. These signaling scaffold complexes may function to regulate receptor phosphorylation in synaptic plasticity. Thus, it is important to understand regulation of AKAP79/150 targeting to synapses and recruitment to PSD-MAGUK complexes. AKAP79 is targeted to the plasma membrane by an N-terminal basic domain that binds phosphatidylinositol-4,5-bisphosphate (PI-4,5-P(2)) and is regulated by PKC phosphorylation and calmodulin binding. Here we demonstrate that this same domain also binds F-actin in a calmodulin- and PKC-regulated manner, targets to membrane ruffles enriched in F-actin and PI-4,5-P(2) in COS7 cells, and localizes to dendritic spines with F-actin and PSD-MAGUKs in hippocampal neurons. Inhibition of actin polymerization disrupted AKAP79 targeting of PKA and CaN to ruffles in COS7 cells and endogenous AKAP79/150 dendritic spine localization with PKA, CaN, and PSD-MAGUKs in neurons. AKAP79/150 postsynaptic localization was rapidly regulated by NMDA receptors through CaN activation and F-actin remodeling, further suggesting that AKAP79/150 signaling scaffold targeting depends on actin dynamics. NMDA receptor activation also regulated dendritic spine localization of PKA and CaN and association of the AKAP79/150-PKA complex with PSD-MAGUKs. Because AMPA receptor PKA phosphorylation and synaptic localization are regulated by similar NMDA receptor-CaN signaling pathways linked to hippocampal long-term depression, this regulation of AKAP79/150 postsynaptic targeting might be important for synaptic plasticity.

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Authors: Gomez, L. L., Alam, S., Smith, K. E., Horne, E., & Dell'Acqua, M. L.
ORCID: Horne, Eric
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2002-08-15
Volume: 22
Issue: 16
Pages: 7027-7044
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.22-16-07027.2002
PMC: PMC6757891
OpenAlex: W2101875004
Cited by: 170
References: 68
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 8 · 2014: 11 · 2013: 8 · 2012: 11
FWCI: 4.08
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Heart Association
National Institutes of Health (NS40701)
National Institute of Neurological Disorders and Stroke (R56NS040701, R01NS040701)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: AKAP79/150, protein kinase A, calcineurin, NMDA receptor signaling, F-actin binding, phosphatidylinositol 4,5-bisphosphate, calmodulin, protein kinase C, dendritic spines, ruffles, synaptic plasticity, hippocampal neurons, AMPA receptor phosphorylation
MeSH terms: Disks Large Homolog 4 Protein, Actins, Animals, Carrier Proteins, Cells, Cultured, Dendrites, Membrane Proteins, Nerve Tissue Proteins, Neurons, Peptide Fragments, Protein Binding, Synapses, Transfection, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Protein Structure, Tertiary, Cyclic AMP-Dependent Protein Kinases, Receptors, AMPA, COS Cells, Calcineurin, Protein Transport, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Rats, A Kinase Anchor Proteins

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Regulation of A-kinase anchoring protein 79/150-cAMP-dependent protein kinase postsynaptic targeting by NMDA receptor activation of calcineurin and remodeling of dendritic actin

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