Abstract
Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases.
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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Antibodies / pharmacology
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Bucladesine / pharmacology
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Cells, Cultured
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Conserved Sequence
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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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Embryo, Nonmammalian
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Enzyme Activators / pharmacology
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Enzyme Inhibitors / pharmacology
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Genes, Reporter
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Microinjections
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Neurites / drug effects
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Neurites / metabolism
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism*
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Phosphorylation / drug effects
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RNA, Messenger / pharmacology
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Sequence Homology, Amino Acid
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Synapsins / antagonists & inhibitors
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Synapsins / genetics
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Synapsins / metabolism*
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Xenopus laevis
Substances
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Antibodies
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Enzyme Activators
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Enzyme Inhibitors
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RNA, Messenger
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Synapsins
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Bucladesine
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Cyclic AMP-Dependent Protein Kinases