A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth

Hung Teh Kao; Hong Jun Song; Barbara Porton; Guo Li Ming; Josephine Hoh; Michael Abraham; Andrew J. Czernik; Vincent A. Pieribone; Mu Ming Poo; Paul Greengard

doi:10.1038/nn840

A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth

Hung Teh Kao, Hong Jun Song, Barbara Porton, Guo Li Ming, Josephine Hoh, Michael Abraham, Andrew J. Czernik, Vincent A. Pieribone, Mu Ming Poo, Paul Greengard

Research output: Contribution to journal › Article › peer-review

125 Scopus citations

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.

Original language	English (US)
Pages (from-to)	431-437
Number of pages	7
Journal	Nature Neuroscience
Volume	5
Issue number	5
DOIs	https://doi.org/10.1038/nn840
State	Published - 2002
Externally published	Yes

ASJC Scopus subject areas

Neuroscience(all)

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10.1038/nn840

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title = "A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth",

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.",

author = "Kao, {Hung Teh} and Song, {Hong Jun} and Barbara Porton and Ming, {Guo Li} and Josephine Hoh and Michael Abraham and Czernik, {Andrew J.} and Pieribone, {Vincent A.} and Poo, {Mu Ming} and Paul Greengard",

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AU - Kao, Hung Teh

AU - Song, Hong Jun

AU - Porton, Barbara

AU - Ming, Guo Li

AU - Hoh, Josephine

AU - Abraham, Michael

AU - Czernik, Andrew J.

AU - Pieribone, Vincent A.

AU - Poo, Mu Ming

AU - Greengard, Paul

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

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A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth

Abstract

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