Signalling pathways underlying neural cell adhesion molecule-mediated survival of dopaminergic neurons.

Stimulation of the neural cell adhesion molecule (NCAM) by homophilic interactions is known to lead to neurite outgrowth as well as to neuronal survival. Whereas a complex network of signalling molecules is known to be of importance to NCAM-mediated neurite extension, only limited information is available regarding signalling underlying NCAM-mediated neuroprotection. Here, we present data suggesting a difference in the signalling events required for survival of rat dopaminergic neurons as compared with neurite outgrowth from the same cell type. Whereas Fyn, fibroblast growth factor receptor, mitogen-activated protein and ERK kinase, protein kinase A and protein kinase C are required for both responses to NCAM-induced signalling, phospholipase C and Ca(2+)-calmodulin-dependent kinase II are only necessary for the neurite outgrowth response, but dispensable for neuroprotection.