Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex.

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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Binding, Competitive, Blotting, Western, Carrier Proteins, Cyclic AMP-Dependent Protein Kinases, Guanylate Kinase, Hippocampus, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Microscopy, Confocal, Nerve Tissue Proteins, Neurons, Nucleoside-Phosphate Kinase, Precipitin Tests, Protein Binding, Rats, Receptors, AMPA, Receptors, Glutamate, Receptors, N-Methyl-D-Aspartate, Signal Transduction, Synaptic Transmission
Neuron
Date: Jul. 01, 2000
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