Mouse semaphorin H induces PC12 cell neurite outgrowth activating Ras-mitogen-activated protein kinase signaling pathway via Ca(2+) influx.
We recently showed that mouse semaphorin H (MSH), a secreted semaphorin molecule, acts as a chemorepulsive factor on sensory neurites. In this study, we found for the first time that MSH induces neurite outgrowth in PC12 cells in a dose-dependent manner. Comparison of Ras-mitogen-activated protein kinase (MAPK) signaling pathways between MSH and nerve growth factor (NGF) revealed that these pathways are crucial for MSH action as well as NGF. K-252a, an inhibitor of tyrosine autophosphorylation of tyrosine kinase receptors (Trks), did not inhibit the action of MSH, suggesting that MSH action occurs via a different receptor than NGF. L- and N-types of voltage-dependent Ca(2+) channel blockers, diltiazem and omega-conotoxin, inhibited MSH-induced neurite outgrowth and MAPK phosphorylation in a Ca(2+)-dependent manner. A transient elevation in intracellular Ca(2+) level was observed upon MSH stimulation. These findings suggest that extracellular Ca(2+) influx, followed by activation of the Ras-MAPK signaling pathway, is required for MSH induced PC12 cell neurite outgrowth.
Sakai
T
T
Group of Neurobiology, School of Allied Health Sciences, Osaka University Faculty of Medicine, Yamadaoka 1-7, Suita-shi, Osaka, 565-0871, Japan.
Furuyama
T
T
Ohoka
Y
Y
Miyazaki
N
N
Fujioka
S
S
Sugimoto
H
H
Amasaki
M
M
Hattori
S
S
Matsuya
T
T
Inagaki
S
S
D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins; D006801:Humans; D017136:Ion Transport; D020935:MAP Kinase Signaling System; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016501:Neurites; D016716:PC12 Cells; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D039961:Semaphorins; D018631:ras Proteins / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C111150:Sema3e protein, mouse; D039961:Semaphorins; D009074:Melanocyte-Stimulating Hormones; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D018631:ras Proteins; D002118:Calcium