Abstract
We report that CaM kinase IV and CREB play a critical role in mediating calcium-induced dendritic growth in cortical neurons. Calcium-dependent dendritic growth is suppressed by CaM kinase inhibitors, a constitutively active form of CaM kinase IV induces dendritic growth in the absence of extracellular stimulation, and a kinase-dead form of CaM kinase IV suppresses dendritic growth induced by calcium influx. CaM kinase IV activates the transcription factor CREB, and expression of a dominant negative form of CREB blocks calcium- and CaM kinase IV-induced dendritic growth. In cortical slice cultures, dendritic growth is attenuated by inhibitors of voltage-sensitive calcium channels and by dominant negative CREB. These experiments indicate that calcium-induced dendritic growth is regulated by activation of a transcriptional program that involves CaM kinase IV and CREB-mediated signaling to the nucleus.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Calcium / physiology*
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
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Calcium-Calmodulin-Dependent Protein Kinases / physiology*
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Cell Division / drug effects
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Cell Division / genetics
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Cell Division / physiology
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Cells, Cultured
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Cerebral Cortex / cytology
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Cerebral Cortex / drug effects
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Cerebral Cortex / enzymology
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Cyclic AMP Response Element-Binding Protein / physiology*
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Dendrites / drug effects
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Dendrites / metabolism*
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Rats
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Rats, Long-Evans
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Transcription, Genetic / drug effects
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Transcription, Genetic / physiology*
Substances
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Calcium-Calmodulin-Dependent Protein Kinase Type 4
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Calcium-Calmodulin-Dependent Protein Kinases
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Camk4 protein, rat
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Calcium