Cell calcium signaling via GM1 cell surface gangliosides in the human Jurkat T cell line

J Immunol. 1994 Apr 1;152(7):3271-81.

Abstract

The cell surface ganglioside GM1 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 Ca2+ concentration can be elicited by using B subunits to ligate GM1 molecules. This Ca2+ signaling effect is clearly mediated through GM1 because it can be observed after direct insertion of exogenous GM1 in a Jurkat cell variant deficient in GM1 expression. The observed Ca2+ response clearly involves both the release of Ca2+ from intracellular stores and a Ca2+ influx from extracellular spaces. It is sustained in the presence of 1 mM extracellular Ca2+, whereas it becomes transient in Ca(2+)-free medium. We show that the GM1-mediated stimulation partially empties the CD3-dependent and inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ pool suggesting a dependence of the Ca2+ 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 GM1. GM1 stimulation results in an IL-2 production comparable to that obtained after CD3 activation. Finally, the GM1-linked cell Ca2+ 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 GM1-induced cell Ca2+ response. Altogether, these data show that cell surface gangliosides GM1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD3 Complex / physiology
  • Calcium / physiology*
  • Cholera Toxin / pharmacology
  • G(M1) Ganglioside / physiology*
  • Humans
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation
  • Phosphotyrosine
  • Receptors, Antigen, T-Cell / physiology
  • Signal Transduction
  • T-Lymphocytes / physiology*
  • Tumor Cells, Cultured
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

  • CD3 Complex
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • Phosphotyrosine
  • G(M1) Ganglioside
  • Tyrosine
  • Cholera Toxin
  • Calcium