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

EMBO J. 2007 Nov 28;26(23):4879-90. doi: 10.1038/sj.emboj.7601884. Epub 2007 Nov 1.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • A Kinase Anchor Proteins / metabolism
  • A Kinase Anchor Proteins / physiology*
  • Aging
  • Animals
  • Calcium / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Hippocampus / metabolism
  • Long-Term Potentiation*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphorylation
  • Receptors, AMPA / metabolism*
  • Synapses / metabolism
  • Time Factors


  • A Kinase Anchor Proteins
  • Akap5 protein, mouse
  • Receptors, AMPA
  • Cyclic AMP-Dependent Protein Kinases
  • glutamate receptor ionotropic, AMPA 2
  • Calcium