Galanin and galanin-like peptide modulate neurite outgrowth via protein kinase C-mediated activation of extracellular signal-related kinase.
The neuropeptide galanin is widely distributed in the central nervous system and plays a role in a number of processes in the adult brain. Galanin also has neurotrophic effects in the developing nervous system and after nerve injury. The current study investigated the mechanism by which galanin promotes neurite outgrowth in the neuronal cell line PC12 and in neurospheres derived from adult hippocampal progenitor cells. We demonstrated that galanin can induce extracellular signal-related kinase (ERK) phosphorylation transiently in a concentration-dependent manner in neurons. Galanin-like peptide, which is thought to signal primarily through the GalR2 receptor subtype, induced ERK phosphorylation with similar kinetics to galanin. In functional studies, the ability of galanin and galanin-like peptide to induce neurite outgrowth was dependent on activation of both protein kinase C and ERK. This study identified a novel physiological role for galanin-induced ERK phosphorylation and identified ERK and protein kinase C as important signaling components in the galanin-mediated modulation of neurite outgrowth.
Hawes
Jessica J
JJ
Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd floor research, New Haven, CT 06508, USA.
Narasimhaiah
Roopashree
R
Picciotto
Marina R
MR
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D019004:Galanin / Q000494:pharmacology*; D044089:Galanin-Like Peptide / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044088:Receptors, Galanin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects
D004791:Enzyme Inhibitors; D044089:Galanin-Like Peptide; D012333:RNA, Messenger; D044088:Receptors, Galanin; D019004:Galanin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases