A cyclic AMP-regulated negative feedforward system for neuritogenesis revealed in a neuroblastomaxglioma hybrid cell line.
We examined the role of second messengers during the neuritogenesis that accompanies neuronal differentiation in a neuroblastomaxglioma hybrid cell line (NG108-15). NG108-15 cells extended neurites after treatment with dibutyryl cyclic AMP. This dibutyryl cyclic AMP treatment evoked the synthesis of voltage-dependent Ca(2+) channel proteins in the cells. The number of neurites was decreased by Ca(2+) influx under condition of high K(+). Interestingly, the increase of neurites stimulated by dibutyryl cyclic AMP and the decrease of neurites caused by high K(+) were both reversible. This is the first study to demonstrate that cyclic AMP regulates a negative feedforward system for neuritogenesis, which links with Ca(2+) signaling. Such a dual role of cyclic AMP may play an important part in precise neurite targeting.
Tojima
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Division of Biological Sciences, Graduate School of Science, Hokkaido University, 060-0810, Sapporo, Japan.
Ito
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002678:Chimera / Q000378:metabolism; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D016257:Fura-2 / Q000493:pharmacokinetics; D005910:Glioma; D007150:Immunohistochemistry; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009447:Neuroblastoma; D011189:Potassium Chloride / Q000493:pharmacokinetics; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D005456:Fluorescent Dyes; D003994:Bucladesine; D011189:Potassium Chloride; D000242:Cyclic AMP; D016257:Fura-2