CA2-CADHERIN AND LAMININ( INFLUX AND NEURITE GROWTH IN RESPONSE TO PURIFIED N)

The signaling mechanisms underlying neu rite growth induced by cadheri ns and integrins are incompletely understood. In our experiments, we h ave examined these mechanisms using purified N-cadherin and laminin (L N). We find that unlike the neurite growth induced by fibroblastic cel ls expressing transfected N-cadherin (Doherty, P., and F. S. Walsh. 19 92. Curr. Opin. Neurobiol. 2:595-601), growth induced by purified N-ca dherin in chick ciliary ganglion (CG), sensory, or forebrain neurons i s not sensitive to inhibition by pertussis toxin. Using fura-2 imaging of single cells, we show that soluble N-cadherin induces Ca2+ increas es in CG neuron cell bodies, and, importantly, in growth cones. In con trast, N-cadherin can induce Ca2+ decreases in glial cells. N-cadherin -induced neuronal Ca2+ responses are sensitive to Ni2+ but are relativ ely insensitive to diltiazem and omega-conotoxin. Similarly, neurite g rowth induced by purified N-cadherin is inhibited-by Ni2+, but is unaf fected by diltiazem and conotoxin. Soluble LN also induced small Ca2responses in CG neurons. LN-induced neurite growth, like that induced by N-cadherin, is insensitive to diltiazem and conotoxin, but is highl y sensitive to Ni2+ inhibition. K+ depolarization experiments suggest that voltage-dependent Ca2+ influx pathways in CG neurons (cell bodies and growth cones) are largely blocked by the combination of diltiazem and Ni2+, Our results demonstrate that cadherin signaling involves ce ll type-specific Ca2+ changes in responding cells, and in particular, that N-cadherin can cause Ca2+ increases in neuronal growth cones. Our findings are consistent with the current idea that distinct neuronal transduction pathways exist for cell adhesion molecules compared with integrins, but suggest that the involvement of Ca2+ signals in both of these pathways is more complex than previously appreciated.