Targeting of PKA to Glutamate Receptors through a MAGUK-AKAP Complex
Open accessAbstract
Compartmentalization of glutamate receptors with the signaling enzymes that regulate their activity supports synaptic transmission. Two classes of binding proteins organize these complexes: the MAGUK proteins that cluster glutamate receptors and AKAPs that anchor kinases and phosphatases. In this report, we demonstrate that glutamate receptors and PKA are recruited into a macromolecular signaling complex through direct interaction between the MAGUK proteins, PSD-95 and SAP97, and AKAP79/150. The SH3 and GK regions of the MAGUKs mediate binding to the AKAP. Cell-based studies indicate that phosphorylation of AMPA receptors is enhanced by a SAP97-AKAP79 complex that directs PKA to GluR1 via a PDZ domain interaction. As AMPA receptor phosphorylation is implicated in regulating synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be centrally involved.
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Through its linkage by PSD-95 family MAGUKs, AKAP150-anchored CaN is targeted near the C-termini of AMPARs and NMDARs, where it is optimally positioned to respond to NMDAR Ca2+ influx during LTD induction.
“Through its linkage by PSD-95 family MAGUKs (Colledge et al., 2000), AKAP150-anchored CaN is targeted near the C-termini of AMPARs and NMDARs, where it is optimally positioned to respond to NMDAR Ca2+ influx during LTD induction.”
From AKAP150-Anchored Calcineurin Regulates Synaptic Plasticity by Limiting Synaptic Incorporation of Ca<sup>2+</sup>-Permeable AMPA Receptors (2012) · cites this paper as Colledge et al., 2000
The paper supports a linkage between AKAP79/150 and PSD-95 family MAGUKs, but not the claimed targeting of AKAP150-anchored calcineurin (CaN) through that linkage. Its Discussion (page unavailable) reports that PSD-95 competes with calcineurin for AKAP79/150 binding and suggests that MAGUK-bound AKAP79/150 preferentially targets kinases, not phosphatases, to glutamate receptors. (LLM, conf=0.88)
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- Authors
- Colledge, M., Dean, R. A., Scott, G. K., Langeberg, L. K., Huganir, R. L., & Scott, J. D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Scott, John D
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2000-07
- Volume
- 27
- Issue
- 1
- Pages
- 107-119
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1964330366
- Cited by
- 467
- References
- 2
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 12 · 2018: 7 · 2017: 18 · 2016: 9 · 2015: 15 · 2014: 23 · 2013: 13 · 2012: 26
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM-48231)
- 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 › Receptor Mechanisms and Signaling
- Keywords
- protein kinase A, glutamate receptors, MAGUK proteins, AKAP79/150, PSD-95, SAP97, AMPA receptor phosphorylation, GluR1, PDZ domain, SH3 domain, signaling complexes, synaptic plasticity
- MeSH terms
- Disks Large Homolog 4 Protein, Animals, Binding, Competitive, Carrier Proteins, Hippocampus, Immunohistochemistry, Membrane Proteins, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Nucleoside-Phosphate Kinase, Precipitin Tests, Protein Binding, Blotting, Western, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Cyclic AMP-Dependent Protein Kinases, Receptors, AMPA, Microscopy, Confocal, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Rats, Guanylate Kinases
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