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 journalArticle

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 languageEnglish (US)
Pages (from-to)431-437
Number of pages7
JournalNature Neuroscience
Volume5
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kao, H. T., Song, H. J., Porton, B., Ming, G. L., Hoh, J., Abraham, M., Czernik, A. J., Pieribone, V. A., Poo, M. M., & Greengard, P. (2002). A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth. Nature Neuroscience, 5(5), 431-437. https://doi.org/10.1038/nn840