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

doi:10.1074/jbc.M111.254912

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A kinase anchor protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density

Journal article

Open access

Peer reviewed

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 and Johannes W Hell

The Journal of biological chemistry, Vol.286(30), pp.26496-26506

07/29/2011

DOI: 10.1074/jbc.M111.254912

PMCID: PMC3143614

PMID: 21652711

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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.

Cyclic AMP-Dependent Protein Kinases - metabolism

Pyramidal Cells - cytology

Dendrites - metabolism

Pyramidal Cells - metabolism

Spinal Cord - metabolism

Inhibitory Postsynaptic Potentials - physiology

Male

Hippocampus - cytology

Mice, Knockout

Excitatory Postsynaptic Potentials - physiology

A Kinase Anchor Proteins - genetics

Hippocampus - metabolism

Animals

Cyclic AMP-Dependent Protein Kinases - genetics

Aging - physiology

Mice

Spinal Cord - cytology

A Kinase Anchor Proteins - metabolism

Details

Title: Subtitle: A kinase anchor protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density
Creators: Yuan Lu - Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. luyuan@mail.nih.gov
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
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.286(30), pp.26496-26506
DOI: 10.1074/jbc.M111.254912
PMID: 21652711
PMCID: PMC3143614
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 GM032875 / NIGMS NIH HHS NS057714 / NINDS NIH HHS R56 NS056244 / NINDS NIH HHS R01 NS043254 / NINDS NIH HHS GM032875 / NIGMS NIH HHS Z99 HD999999 / Intramural NIH HHS R01 NS057714 / NINDS NIH HHS R01 NS035563 / NINDS NIH HHS NS017502 / NINDS NIH HHS NS035563 / NINDS NIH HHS P01 DA015916 / NIDA NIH HHS S10 RR017941 / NCRR NIH HHS R01 AG017502 / NIA NIH HHS DC002961 / NIDCD NIH HHS R01 DC002961 / NIDCD NIH HHS NS043254 / NINDS NIH HHS R01 NS056244 / NINDS NIH HHS DA015916 / NIDA NIH HHS NS056244 / NINDS NIH HHS R01 DC009405 / NIDCD NIH HHS
Language: English
Date published: 07/29/2011
Academic Unit: Pathology; Iowa Neuroscience Institute; Cardiovascular Medicine; Biology; Neuroscience and Pharmacology; Otolaryngology; Internal Medicine
Record Identifier: 9983991996302771

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