Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels.
We present evidence that the morphoregulatory activities of neural cell adhesion molecule (NCAM) and N-cadherin involve activation of intracellular second messenger pathways. PC12 cells were cultured on monolayers of control 3T3 cells or 3T3 cells expressing transfected N-cadherin or NCAM. NCAM and N-cadherin directly induced a transcription-independent change in the morphology of PC12 cells from an adrenal to neuronal phenotype and also specifically increased Thy-1, but not L1/NILE or low affinity NGF receptor, immunoreactivity. The morphological response was more rapid and, in the case of N-cadherin, more substantial than that induced by NGF. It could be fully inhibited by pertussis toxin and a combination of L- and N-type Ca2+ channel antagonists, but not by broad-specificity kinase inhibitors. It was blocked, however, by the kinase inhibitor K-252b. These studies suggest that cell adhesion molecules directly alter cell phenotype and provide direct evidence for transmembrane signaling mediating both the morphological and biochemical responses induced by NCAM and N-cadherin.
Department of Experimental Pathology, UMDS, Guy's Hospital, London, England.
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Doherty
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Ashton
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Moore
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Walsh
D016475:3T3 Cells; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D015820:Cadherins / Q000235:genetics / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D037342:Pertussis Toxin; D047428:Protein Kinase Inhibitors; D018800:Thy-1 Antigens; D014158:Transcription, Genetic; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000954:Antigens, Surface; D015820:Cadherins; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; D047428:Protein Kinase Inhibitors; D018800:Thy-1 Antigens; D010566:Virulence Factors, Bordetella; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins