title: Essential role for synaptopodin in dendritic spine plasticity of the developing hippocampus.
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.
authors.affiliation: Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York 10595, USA.
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Zhang
authors.forename: Beatrice
authors.initials: B
authors.lastname: Pöschel
authors.forename: Christian
authors.initials: C
authors.lastname: Faul
authors.forename: Chirag
authors.initials: C
authors.lastname: Upreti
authors.forename: Patric K
authors.initials: PK
authors.lastname: Stanton
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology*; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D018690:Excitatory Amino Acid Agonists; D007546:Isoquinolines; D008840:Microfilament Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C503968:Synpo protein, mouse; D016202:N-Methylaspartate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide