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.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
authors.forename: Hung-Teh
authors.initials: HT
authors.lastname: Kao
authors.forename: Hong-jun
authors.initials: HJ
authors.lastname: Song
authors.forename: Barbara
authors.initials: B
authors.lastname: Porton
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Josephine
authors.initials: J
authors.lastname: Hoh
authors.forename: Michael
authors.initials: M
authors.lastname: Abraham
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Czernik
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Pieribone
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D017124:Conserved Sequence; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter; D008845:Microinjections; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D016704:Synapsins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D000906:Antibodies; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016704:Synapsins; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases