John Libbey Eurotext

Magnesium Research


Loss of MAGT1 abrogates the Mg 2+ flux required for T cell signaling and leads to a novel human primary immunodeficiency Volume 24, numéro 3, September 2011

Molecular Development Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, Biomedical Sciences Graduate Program, University of California-San Francisco, San Francisco, CA, USA
  • Mots-clés : immunology, signaling, magnesium, disease, MAGT1
  • DOI : 10.1684/mrh.2011.0286
  • Page(s) : 109-14
  • Année de parution : 2011

Although Mg 2+ has a well-recognized role as an essential cofactor for all ATP-binding enzymes, its role as a signaling ion, like Ca 2+, has been controversial. A requirement for Mg 2+ for optimal T lymphocyte stimulation was demonstrated more than 30 years ago, but the mechanism of its synergistic effect with Ca 2+ in T cell activation remains elusive. Here, we summarize our recent discovery of a signaling role for Mg 2+ in the T cell antigen receptor (TCR) signaling pathway from the study of a novel primary immunodeficiency, now named X-linked immunodeficiency with Mg 2+ defect, EBV infection and neoplasia (XMEN). XMEN patients were found to have a deficiency in magnesium transporter 1 (MAGT1), an Mg 2+-specific transporter, which leads to the absence of a TCR-stimulated Mg 2+ flux and an attenuation of T cell activation. We further showed that this Mg 2+ flux is required proximally for the temporal orchestration of phospholipase C-γ1 (PLCγ1) activation. Thus, our study not only provides a second messenger role for Mg 2+ to explain its synergism with calcium in T cell signaling, it also identifies a potential extracellular therapeutic target for T cell-specific immunomodulation.