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

Yuan Lu, Margaret Allen, Amy R. Halt, Michael Weisenhaus, Robert F. Dallapiazza, Duane D. Hall, Yuriy M. Usachev, G. Stanley McKnight, Johannes W Hell

Research output: Contribution to journalArticle

127 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4879-4890
Number of pages12
JournalEMBO Journal
Volume26
Issue number23
DOIs
StatePublished - Nov 28 2007
Externally publishedYes

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Keywords

  • AKAP
  • AMPA receptors
  • Calcium
  • PKA
  • Synapse

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Lu, Y., Allen, M., Halt, A. R., Weisenhaus, M., Dallapiazza, R. F., Hall, D. D., Usachev, Y. M., McKnight, G. S., & Hell, J. W. (2007). Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. EMBO Journal, 26(23), 4879-4890. https://doi.org/10.1038/sj.emboj.7601884