Neurotrophic effect of Semaphorin 4D in PC12 cells.
Semaphorins provide crucial attractive and repulsive cues involved in axon guidance during neural development. Out of them, Semaphorin 4D (Sema4D) is enriched in the nervous and immune tissues, and acts as proliferative and survival factors of peripheral lymphocytes in the immune system, but is poorly understood in the nervous system. By using PC12 cells which are well known to differentiate into neural cells in response to nerve growth factor (NGF), we found that soluble forms of Sema4D had neurotrophic effects which were inhibited by neutralizing antibodies to Sema4D. Sema4D strikingly potentiated neurite outgrowth in the presence of 50 ng/ml NGF and increased sensitivity to NGF. Cells responded to very low concentrations of NGF in the presence of 1 nM Sema4D. Activation of following signal proteins, protein kinase C (PKC), L-type of voltage-dependent Ca(2+) channel, and phosphatidylinositol (PI) 3-kinase mediated neurotrophic neurite-outgrowth action of Sema4D. These findings suggest a new function of Sema4D as a neurotrophic signal in PC12 cells.
Fujioka
Shiho
S
Group of Neurobiology, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Yamadaoka 1-7, Suita-shi, Osaka 565-0871, Japan.
Masuda
Kenta
K
Toguchi
Marcia
M
Ohoka
Yoshiharu
Y
Sakai
Takayoshi
T
Furuyama
Tatsuo
T
Inagaki
Shinobu
S
D000818:Animals; D015703:Antigens, CD; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D016716:PC12 Cells; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D039961:Semaphorins; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D015703:Antigens, CD; C093224:CD100 antigen; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005419:Flavonoids; D008562:Membrane Glycoproteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D039961:Semaphorins; D020932:Nerve Growth Factor; D011493:Protein Kinase C; D018631:ras Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one