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

Nat Neurosci. 2002 May;5(5):431-7. doi: 10.1038/nn840.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Bucladesine / pharmacology
  • Cells, Cultured
  • Conserved Sequence
  • Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Embryo, Nonmammalian
  • Enzyme Activators / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Genes, Reporter
  • Microinjections
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Neurites / drug effects
  • Neurites / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Phosphorylation / drug effects
  • RNA, Messenger / pharmacology
  • Sequence Homology, Amino Acid
  • Synapsins / antagonists & inhibitors
  • Synapsins / genetics
  • Synapsins / metabolism*
  • Xenopus laevis


  • Antibodies
  • Enzyme Activators
  • Enzyme Inhibitors
  • RNA, Messenger
  • Synapsins
  • Bucladesine
  • Cyclic AMP-Dependent Protein Kinases