A single pulse of nerve growth factor triggers long-term neuronal excitability through sodium channel gene induction.
The continuous presence of nerve growth factor (NGF) is thought to be required for the elaboration of neuronal-like traits in PC12 cells. Surprisingly, we find that a 1 min exposure to NGF is sufficient to engage a longer-term genetic program leading to the acquisition of membrane excitability. Whereas continuous exposure to NGF causes the induction of a family of sodium channels, the effect of a brief exposure is to induce selectively expression of the peripheral nerve-type sodium channel gene PN1, through a distinct signaling pathway requiring immediate-early genes. A 1 min exposure of PC12 cells to interferon-gamma also causes PN1 gene induction, suggesting that the "triggered" NGF and interferon-gamma signaling pathways share common molecular intermediates.
Toledo-Aral
J J
JJ
Department of Neurobiology and Behavior State University of New York at Stony Brook 11794-5230.
Brehm
P
P
Halegoua
S
S
Mandel
G
G
D000818:Animals; D015152:Blotting, Northern; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010525:Peripheral Nerves / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D015222:Sodium Channels / Q000096:biosynthesis*; D013997:Time Factors
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015222:Sodium Channels; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D007371:Interferon-gamma