Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.
Association of PKA with the AMPA receptor GluR1 subunit via the A kinase anchor protein AKAP150 is crucial for GluR1 phosphorylation. Mutating the AKAP150 gene to specifically prevent PKA binding reduced PKA within postsynaptic densities (>70%). It abolished hippocampal LTP in 7-12 but not 4-week-old mice. Inhibitors of PKA and of GluR2-lacking AMPA receptors blocked single tetanus LTP in hippocampal slices of 8 but not 4-week-old WT mice. Inhibitors of GluR2-lacking AMPA receptors also prevented LTP in 2 but not 3-week-old mice. Other studies demonstrate that GluR1 homomeric AMPA receptors are the main GluR2-lacking AMPA receptors in adult hippocampus and require PKA for their functional postsynaptic expression during potentiation. AKAP150-anchored PKA might thus critically contribute to LTP in adult hippocampus in part by phosphorylating GluR1 to foster postsynaptic accumulation of homomeric GluR1 AMPA receptors during initial LTP in 8-week-old mice.
Lu
Yuan
Y
Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242-1109, USA.
Allen
Margaret
M
Halt
Amy R
AR
Weisenhaus
Michael
M
Dallapiazza
Robert F
RF
Hall
Duane D
DD
Usachev
Yuriy M
YM
McKnight
G Stanley
GS
Hell
Johannes W
JW
D054758:A Kinase Anchor Proteins / Q000378:metabolism / Q000502:physiology*; D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D017774:Long-Term Potentiation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse; D018091:Receptors, AMPA; D017868:Cyclic AMP-Dependent Protein Kinases; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium