A Kinase Anchor Protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density

Yuan Lu, Xiang Ming Zha, Eun Young Kim, Scott Schachtele, Michael E. Dailey, Duane D. Hall, Stefan Strack, Steven H. Green, Dax A. Hoffman, Johannes W Hell

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The A kinase anchor protein AKAP150 recruits the cAMP-dependent protein kinase (PKA) to dendritic spines. Here we show that in AKAP150 (AKAP5) knock-out (KO) mice frequency of miniature excitatory post-synaptic currents (mEPSC) and inhibitory post-synaptic currents (mIPSC) are elevated at 2 weeks and, more modestly, 4 weeks of age in the hippocampal CA1 area versus litter mate WT mice. Linear spine density and ratio of AMPAR to NMDAR EPSC amplitudes were also increased. Amplitude and decay time of mEPSCs, decay time of mIPSCs, and spine size were unaltered. Mice in which the PKA anchoring C-terminal 36 residues of AKAP150 are deleted (D36) showed similar changes. Furthermore, whereas acute stimulation of PKA (2- 4 h) increases spine density, prolonged PKA stimulation (48 h) reduces spine density in apical dendrites of CA1 pyramidal neurons in organotypic slice cultures. The data from the AKAP150 mutant mice show that AKAP150-anchored PKA chronically limits the number of spines with functional AMPARs at 2-4 weeks of age. However, synaptic transmission and spine density was normal at 8 weeks in KO and D36 mice. Thus AKAP150-independent mechanisms correct the aberrantly high number of active spines in juvenile AKAP150 KO and D36 mice during development.

Original languageEnglish (US)
Pages (from-to)26496-26506
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number30
DOIs
StatePublished - Jul 29 2011

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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    Lu, Y., Zha, X. M., Kim, E. Y., Schachtele, S., Dailey, M. E., Hall, D. D., Strack, S., Green, S. H., Hoffman, D. A., & Hell, J. W. (2011). A Kinase Anchor Protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density. Journal of Biological Chemistry, 286(30), 26496-26506. https://doi.org/10.1074/jbc.M111.254912