Ganglioside modulation of neural cell adhesion molecule and N-cadherin-dependent neurite outgrowth.
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 neurite 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 micrograms/ml) in the co-culture was associated with a potentiation of NCAM and N-cadherin-dependent neurite outgrowth. Treatment of PC12 cells with GM1 (100 micrograms/ml) for 90 min led to trypsin-stable increases in both beta-cholera toxin binding to PC12 cells and an enhanced neurite 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.
Doherty
P
P
Department of Experimental Pathology, UMDS, Guy's Hospital, London, United Kingdom.
Ashton
S V
SV
Skaper
S D
SD
Leon
A
A
Walsh
F S
FS
D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015820:Cadherins; D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; D010566:Virulence Factors, Bordetella; D005677:G(M1) Ganglioside; D002772:Cholera Toxin; D037342:Pertussis Toxin; D002118:Calcium