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


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  • Auteur(s) : Feng-Yen Li, Michael J. Lenardo, Benjamin Chaigne-Delalande , 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
  • Page(s) : 109-14
  • DOI : 10.1684/mrh.2011.0286
  • 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.