Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Binding, Competitive / physiology
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Blotting, Western
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Carrier Proteins / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism*
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Disks Large Homolog 4 Protein
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Guanylate Kinases
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Hippocampus / cytology
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Hippocampus / metabolism
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Immunohistochemistry
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Microscopy, Confocal
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Nerve Tissue Proteins / physiology
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Neurons / metabolism
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Nucleoside-Phosphate Kinase / metabolism*
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Precipitin Tests
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Protein Binding / physiology
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Rats
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Receptors, AMPA / metabolism
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Receptors, AMPA / physiology
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Receptors, Glutamate / metabolism*
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Receptors, N-Methyl-D-Aspartate / physiology
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Signal Transduction / physiology*
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Synaptic Transmission / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Disks Large Homolog 4 Protein
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Dlg1 protein, rat
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Mpp2 protein, rat
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Nerve Tissue Proteins
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Receptors, AMPA
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Receptors, Glutamate
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Receptors, N-Methyl-D-Aspartate
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postsynaptic density proteins
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Cyclic AMP-Dependent Protein Kinases
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Nucleoside-Phosphate Kinase
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Guanylate Kinases
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glutamate receptor ionotropic, AMPA 1