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Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.


ABSTRACT: 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.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC2099463 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP.

Lu Yuan Y   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  

The EMBO journal 20071101 23


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 prevente  ...[more]

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