title: A kinase anchor protein 150 (AKAP150)-associated protein kinase A limits dendritic spine density.
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.
authors.affiliation: Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. luyuan@mail.nih.gov
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Xiang-ming
authors.initials: XM
authors.lastname: Zha
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.forename: Scott
authors.initials: S
authors.lastname: Schachtele
authors.forename: Michael E
authors.initials: ME
authors.lastname: Dailey
authors.forename: Duane D
authors.initials: DD
authors.lastname: Hall
authors.forename: Stefan
authors.initials: S
authors.lastname: Strack
authors.forename: Steven H
authors.initials: SH
authors.lastname: Green
authors.forename: Dax A
authors.initials: DA
authors.lastname: Hoffman
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism*
chemical_list: D054758:A Kinase Anchor Proteins; C520665:Akap5 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases