Signaling role for Mg2+ revealed by immunodeficiency due to loss of MagT1

The magnesium ion, Mg2+, is essential for all life as a cofactor for ATP, polyphosphates such as DNA and RNA, and metabolic enzymes, but whether it plays a role in intracellular signaling similar to Ca2+ is unknown. In this study, we identify mutations in the magnesium transporter gene, MAGT1, in a novel X-linked human immunodeficiency characterized by CD4 lymphopenia, severe chronic viral infections, and defective T lymphocyte activation. We demonstrate that a rapid transient Mg2+ influx is induced by antigen receptor stimulation in T cells or growth factor Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms Correspondence and requests for materials should be addressed to M.J.L. (lenardo@nih.gov).†These authors contributed equally Author Contributions F-Y.L. characterized the MAGT1 mutations and the TCR activation defect in the patients. B.C.D. characterized the Mg2+ influx and the signaling defects. B.C.D., F-Y.L., H.S. and M.J.L. conceived and planned the experiments a