Direct activation of second messenger pathways mimics cell adhesion molecule-dependent neurite outgrowth.
We present evidence that direct activation of neuronal second messenger pathways in PC12 cells by opening voltage-dependent calcium channels mimics cell adhesion molecule (CAM)-induced differentiation of these cells. PC12 cells were cultured on monolayers of control 3T3 cells or 3T3 cells expressing transfected N-cadherin in the presence of KCl or a calcium channel agonist Bay K 8644. Both potassium depolarization and agonist-induced activation of calcium channels promoted substantial neurite outgrowth from PC12 cells cultured on control 3T3 monolayers and increased neurite outgrowth from those cultured on N-cadherin-expressing 3T3 monolayers. The potassium-induced response could be inhibited by L- and N-type calcium channel antagonists and by kinase inhibitor K-252b but was unaffected by pertussis toxin. In contrast activators of protein kinase C did not stimulate neurite outgrowth, and the neurite outgrowth response induced by activation of protein kinase A was not inhibited by calcium channel antagonists or pertussis toxin. These studies support the postulate that CAM-induced neuronal differentiation involves a specific transmembrane signaling pathway and suggest that activation of this pathway after CAM binding may be more important for the neurite outgrowth response than CAM-dependent adhesion per se.
Saffell
J L
JL
Department of Experimental Pathology, UMDS, Guy's Hospital, London, United Kingdom.
Walsh
F S
FS
Doherty
P
P
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002455:Cell Division; D004789:Enzyme Activation; D026121:Indole Alkaloids; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D015290:Second Messenger Systems; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015820:Cadherins; D002121:Calcium Channel Blockers; D002227:Carbazoles; D015815:Cell Adhesion Molecules; D026121:Indole Alkaloids; D010566:Virulence Factors, Bordetella; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C049985:staurosporine aglycone; D037342:Pertussis Toxin; D011494:Protein Kinases; D011188:Potassium