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.
Howard Hughes Medical Institute, Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
M
M
Colledge
R A
RA
Dean
G K
GK
Scott
L K
LK
Langeberg
R L
RL
Huganir
J D
JD
Scott
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009703:Nucleoside-Phosphate Kinase; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C501119:Dlg1 protein, rat; C501449:Dlg4 protein, rat; C501451:Mpp2 protein, rat; C033652:postsynaptic density proteins