A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth.
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.
Kao
Hung-Teh
HT
Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.
Song
Hong-jun
HJ
Porton
Barbara
B
Ming
Guo-li
GL
Hoh
Josephine
J
Abraham
Michael
M
Czernik
Andrew J
AJ
Pieribone
Vincent A
VA
Poo
Mu-ming
MM
Greengard
Paul
P
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
D000906:Antibodies; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D016704:Synapsins; D003994:Bucladesine; D017868:Cyclic AMP-Dependent Protein Kinases