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

123 Citations (Scopus)

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

Fingerprint

AMPA Receptors
A Kinase Anchor Proteins
Hippocampus
Post-Synaptic Density
Phosphorylation
Tetanus
Genes

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., ... 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

Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. / Lu, Yuan; Allen, Margaret; Halt, Amy R.; Weisenhaus, Michael; Dallapiazza, Robert F.; Hall, Duane D.; Usachev, Yuriy M.; McKnight, G. Stanley; Hell, Johannes W.

In: EMBO Journal, Vol. 26, No. 23, 28.11.2007, p. 4879-4890.

Research output: Contribution to journalArticle

Lu, Y, Allen, M, Halt, AR, Weisenhaus, M, Dallapiazza, RF, Hall, DD, Usachev, YM, McKnight, GS & Hell, JW 2007, 'Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP', EMBO Journal, vol. 26, no. 23, pp. 4879-4890. https://doi.org/10.1038/sj.emboj.7601884
Lu Y, Allen M, Halt AR, Weisenhaus M, Dallapiazza RF, Hall DD et al. Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. EMBO Journal. 2007 Nov 28;26(23):4879-4890. https://doi.org/10.1038/sj.emboj.7601884
Lu, Yuan ; Allen, Margaret ; Halt, Amy R. ; Weisenhaus, Michael ; Dallapiazza, Robert F. ; Hall, Duane D. ; Usachev, Yuriy M. ; McKnight, G. Stanley ; Hell, Johannes W. / Age-dependent requirement of AKAP150-anchored PKA and GluR2-lacking AMPA receptors in LTP. In: EMBO Journal. 2007 ; Vol. 26, No. 23. pp. 4879-4890.
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