A Kinase Anchor Protein 150 (AKAP150)-associated Protein Kinase A Limits Dendritic Spine Density

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 an...

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Bibliographic Details
Published in:The Journal of biological chemistry 2011-07, Vol.286 (30), p.26496-26506
Main Authors: Lu, Yuan, Zha, Xiang-ming, Kim, Eun Young, Schachtele, Scott, Dailey, Michael E., Hall, Duane D., Strack, Stefan, Green, Steven H., Hoffman, Dax A., Hell, Johannes W.
Format: Article
Language:English
Subjects:
A Kinase Anchor Proteins - genetics
A Kinase Anchor Proteins - metabolism
Aging - physiology
AKAP150
Animals
Cyclic AMP-Dependent Protein Kinases - genetics
Cyclic AMP-Dependent Protein Kinases - metabolism
Dendrites - metabolism
Development
Excitatory Postsynaptic Potentials - physiology
Hippocampus - cytology
Hippocampus - metabolism
Inhibitory Postsynaptic Potentials - physiology
Male
Mice
Mice, Knockout
Neurobiology
Protein Kinase A (PKA)
Protein Phosphatase
Pyramidal Cells - cytology
Pyramidal Cells - metabolism
Spinal Cord - cytology
Spinal Cord - metabolism
Spine Density
Spine Formation
Spine Function
Synapses
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M111.254912