Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons

Rosenmund, Christian; Carr, Daniel W.; Bergeson, Susan E.; Nilaver, Gajanan; Scott, John D.; Westbrook, Gary L.

doi:10.1038/368853a0

Cited by 371Neuroscience and Neuropharmacology ResearchProtein Kinase Regulation and GTPase SignalingPhosphodiesterase function and regulation

Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons

Rosenmund, Christian, Carr, Daniel W., Bergeson, Susan E., Nilaver, Gajanan, Scott, John D., Westbrook, Gary L.·1994·Nature

DOI 10.1038/368853a0

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Abstract

Phosphorylation of molecules involved in synaptic transmission by multifunctional protein kinases modulates both pre- and post-synaptic events in the central nervous system. The positioning of kinases near their substrates may be an important part of the regulatory mechanism. The A-kinase-anchoring proteins (AKAPs; ref. 3) are known to bind the regulatory subunit of cyclic AMP-dependent protein kinase A with nanomolar affinity. Here we show that anchoring of protein kinase A by AKAPs is required for the modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate channels. Intracellular perfusion of cultured hippocampal neurons with peptides derived from the conserved kinase binding region of AKAPs prevented the protein kinase A-mediated regulation of AMPA/kainate currents as well as fast excitatory synaptic currents. This effect could be overcome by adding the purified catalytic subunit of protein kinase. A control peptide lacking kinase-binding activity had no effect. To our knowledge, these results provide the first evidence that anchoring of protein kinase A is crucial in the regulation of synaptic function.

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Peptide-mediated inhibition of PKA anchoring or activity caused a very similar decrease in AMPAR currents in hippocampal neurons that was mediated by CaN activation in part by Ca2+ influx through Ca2+-permeable AMPARs.
“peptide-mediated inhibition of PKA anchoring or activity caused a very similar decrease in AMPAR currents in hippocampal neurons that was mediated by CaN activation in part by Ca2+ influx through Ca2+-permeable AMPARs”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca2+-Permeable AMPA Receptors (2012) · cites this paper as Rosenmund et al., 1994

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Authors: Rosenmund, C., Carr, D. W., Bergeson, S. E., Nilaver, G., Scott, J. D., & Westbrook, G. L.
Affiliations: Salk Institute for Biological Studies (US)
Oregon Health & Science University (US)
ORCID: Rosenmund, Christian
Bergeson, Susan E.
Scott, John D.
Westbrook, Gary L.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1994-04
Volume: 368
Issue: 6474
Pages: 853-856
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/368853a0
OpenAlex: W1969039665
Cited by: 371
References: 29
Citations by year: 2026: 1 · 2025: 3 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 6 · 2014: 9 · 2013: 5 · 2012: 13
FWCI: 8.79
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
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 › Phosphodiesterase function and regulation
Keywords: protein kinase A anchoring, A-kinase anchoring proteins, non-NMDA receptors, protein kinase A, hippocampal neurons, synaptic transmission, synaptic modulation
MeSH terms: Animals, Carrier Proteins, Cells, Cultured, Colforsin, Hippocampus, Humans, Membrane Potentials, Neurons, Peptide Fragments, Phosphorylation, Proteins, Synapses, Cyclic AMP-Dependent Protein Kinases, Receptors, AMPA, Kainic Acid Receptors, Adaptor Proteins, Signal Transducing, Rats, A Kinase Anchor Proteins

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Anchoring of protein kinase A is required for modulation of AMPA/kainate receptors on hippocampal neurons

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