Cell calcium signaling via GM1 cell surface gangliosides in the human Jurkat T cell line
Gouy, H.; Deterre, P.; Debré, P.; Bismuth, G.
Journal of Immunology 152(7): 3271-3281
1994
ISSN/ISBN: 0022-1767 PMID: 7511641 Document Number: 431539
The cell surface ganglioside G-M1 is the specific receptor for the B subunit of cholera toxin. We show here that in the human Jurkat T cell line an increase in intracellular free Ca" concentration can be elicited by using B subunits to ligate G-M1 molecules. This Ca-2+ signaling effect is clearly mediated through G-M1 because it can be observed after direct insertion of exogeneous G-M1 in a Jurkat cell variant deficient in G-M1 expression. The observed Ca-2+ response clearly involves both the release of Ca-2+ from intracellular stores and a Ca-2+ influx from extracellular spaces. It is sustained in the presence of 1 mM extracellular Ca", whereas it becomes transient in Ca-2+-free medium. We show that the G-M1-mediated stimulation partially empties the CD3-dependent and inositol 1,4,5 trisphosphate-sensitive intracellular Ca-2+ pool suggesting a dependence of the Ca-2+ response from activation of phospholipase C (PLC) metabolism. Accordingly, tyrosine phosphorylation of PLC-gamma-1 can be evidenced but only in Jurkat cells highly expressing G-M1. G-M1 stimulation results in an IL-2 production comparable to that obtained after CD3 activation. Finally, the G-M1-linked cell Ca-2+ activation pathway is also observed in a Jurkat cell clone lacking Ag-specific receptor expression suggesting that the presence of functional CD3/TCR molecules is not essential for G-M1-induced cell Ca-2+ response. Altogether, these data show that cell surface gangliosides G-M1 may act as a signaling molecule in Jurkat T cells possibly by a new pathway, a finding of importance when considering a possible function for ubiquitous membrane carbohydrate structures in T cell recognition systems.