Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150.
Communication between dopaminergic and glutamatergic synapses is critical for several functions related to cognition and emotion. Here, we examined whether dopamine receptor activity regulates phosphorylation and trafficking of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, GluR1. We find treatment with a dopamine D1 receptor agonist enhanced GluR1 phosphorylation at Ser845, the PKA phosphorylation site, in both striatal and prefrontal cortical neurons. Enhanced phosphorylation of GluR1 also correlated with increased amounts of GluR1 on the cell surface. These effects were disrupted by expression of mutant forms of the A-kinase anchoring protein (AKAP79/150) and the postsynaptic density protein, PSD-95, that fail to target synaptic sites. Similar enhancement of the phosphorylation of GluR1 was observed in the nucleus accumbens upon stimulation of dopamine release in vivo using electrical stimulation of dopamine cell bodies in the ventral tegmental area. These results suggest in vivo stimulation of dopamine release directly influences AMPA receptor phosphorylation and together with in vitro data indicate that coupling of the AMPA receptor to AKAP79/150 and PSD-95 modulate this process.
Department of Psychiatry and the Brain Research Centre, 2255 Wesbrook Mall, University of British Columbia, Vancouver, BC, Canada V6T 1Z3.
Richard D
RD
Swayze
Marie-France
MF
Lisé
Joshua N
JN
Levinson
Anthony
A
Phillips
Alaa
A
El-Husseini
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D004298:Dopamine / Q000502:physiology*; D004622:Embryo, Mammalian; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C415703:Akap5 protein, rat; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D011993:Recombinant Fusion Proteins; C033652:postsynaptic density proteins; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine