Direct Activation of Second Messenger Pathways Mimics Cell Adhesion Molecule-Dependent Neurite Outgrowth

• Published in: The Journal of cell biology 1992-08, Vol.118 (3), p.663-670
• Main Authors: Saffell, Jane L., Walsh, Frank S., Doherty, Patrick
• Format: Article
• Language: English
• Subjects: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; 3T3 Cells; Animals; Biological and medical sciences; Cadherins; Cadherins - physiology; Calcium; Calcium Channel Blockers - pharmacology; Calcium channels; Carbazoles - pharmacology; Cell Adhesion Molecules - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell physiology; Cellular biology; Cultured cells; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Indole Alkaloids; Mice; Molecular and cellular biology; Neural cell adhesion molecules; Neurites; Neurites - drug effects; Neurites - metabolism; Neurites - ultrastructure; Neurons; PC12 Cells; Pertussis Toxin; Potassium - pharmacology; Protein Kinases - metabolism; Second Messenger Systems; Toxins; Virulence Factors, Bordetella - pharmacology; Whooping cough
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.118.3.663

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.