Ganglioside modulation of neural cell adhesion molecule and N-cadherin-dependent neurite outgrowth

Abstract

We have used monolayers of control 3T3 cells and 3T3 cells expressing transfected human neural cell adhesion molecule (NCAM) or chick N-cadherin as a culture substrate for PC12 cells. NCAM and N-cadherin in the monolayer directly promote neunte outgrowth from PC12 cells via a G-protein-dependent activation of neuronal calcium channels. In the present study we show that ganglioside GM1 does not directly activate this pathway in PC12 cells. However, the presence of GM1 (12.5-100 μg/ml) in the co-culture was associated with a potentiation of NCAM and N-cadherin-dependent neunte outgrowth. Treatment of PC12 cells with GM1 (100 μg/ml) for 90 min led to trypsinstable increases in both β-cholera toxin binding to PC12 cells and an enhanced neunte outgrowth response to N-cadherin. The ganglioside response could be fully inhibited by treatment with pertussis toxin. These data are consistent with exogenous gangliosides enhancing neuritic growth by promoting cell adhesion molecule-induced calcium influx into neurons.