A novel, nongenomic mechanism underlies retinoic acid-induced growth cone turning.
The vitamin A metabolite, retinoic acid (RA), is well known for its roles in neural development and regeneration. We have previously shown that RA can induce positive growth cone turning in regenerating neurons in vitro. In this study, we address the subcellular mechanisms underlying this chemo-attractive response, using identified central neurons from the adult mollusc, Lymnaea stagnalis. We show that the RA-induced positive growth cone turning was maintained in the presence of the transcriptional inhibitor, actinomycin D. We also physically transected the neurites from the cell body and showed that isolated growth cones retain the capacity to turn toward a gradient of RA. Moreover, this attractive turning is dependent on de novo local protein synthesis and Ca(2+) influx. Most of RA's actions during neurite outgrowth and regeneration require gene transcription, although these data show for the first time in any species, that the chemotropic action of RA in guiding neurite outgrowth, involves a novel, nongenomic mechanism.
Farrar
Nathan R
NR
Department Biological Sciences, Brock University, St. Catharines, Ontario L2S 3A1, Canada.
Dmetrichuk
Jennifer M
JM
Carlone
Robert L
RL
Spencer
Gaynor E
GE
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D008195:Lymnaea; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002227:Carbazoles; D004791:Enzyme Inhibitors; D011500:Protein Synthesis Inhibitors; D002104:Cadmium; C081021:Go 6976; D003609:Dactinomycin; D014212:Tretinoin; D011493:Protein Kinase C; D002118:Calcium