Abstract
Dendritic spines are a major substrate of brain plasticity. Although many studies have focused on Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-mediated regulation of spine dynamics and synaptic function in adult brain, much less is know about protein kinase A (PKA)-dependent regulation of spine shape dynamics during postnatal brain development. Synaptopodin is a dendritic spine associated modulator of actin dynamics and a substrate of PKA. Here we show that NMDA and cAMP-induced dendritic spine expansion is impaired in hippocampal slices from 15- and 21-d-old synaptopodin-deficient mice. We further show that synaptopodin is required for full expression of PKA-dependent hippocampal long-term potentiation in 15- and 21-d-old, but not adult, mice. PKA-induced cAMP response element-binding phosphorylation is normal in the hippocampus of synaptopodin-deficient mice, suggesting that synaptopodin functions independently of cAMP response element-binding. Our results identify synaptopodin as a substrate of PKA in hippocampal neurons and point to an essential role for synaptopodin in activity-dependent regulation of dendritic spine dynamics and synaptic plasticity in postnatal brain development.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cyclic AMP / metabolism
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Cyclic AMP / pharmacology
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Dendritic Spines / physiology*
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Electrophysiology
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Excitatory Amino Acid Agonists / pharmacology
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Female
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Hippocampus / growth & development*
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Hippocampus / physiology*
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Isoquinolines / pharmacology
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Long-Term Potentiation / physiology
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Male
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Microfilament Proteins / genetics
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Microfilament Proteins / physiology*
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N-Methylaspartate / pharmacology
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Neuronal Plasticity / physiology*
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / physiology
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Protein Kinase Inhibitors / pharmacology
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Substrate Specificity
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Sulfonamides / pharmacology
Substances
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Excitatory Amino Acid Agonists
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Isoquinolines
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Microfilament Proteins
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Protein Kinase Inhibitors
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Sulfonamides
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Synpo protein, mouse
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N-Methylaspartate
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Cyclic AMP
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Cyclic AMP-Dependent Protein Kinases
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide