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- Title
Second messenger role for Mg<sup>2+</sup> revealed by human T-cell immunodeficiency.
- Authors
Feng-Yen Li; Chaigne-Delalande, Benjamin; Kanellopoulou, Chrysi; Davis, Jeremiah C.; Matthews, Helen F.; Douek, Daniel C.; Cohen, Jeffrey I.; Uzel, Gulbu; Su, Helen C.; Lenardo, Michael J.
- Abstract
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 part in intracellular signalling (as Ca2+ does) is unknown. Here 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 normal T cells and by growth factor stimulation in non-lymphoid cells. MAGT1 deficiency abrogates the Mg2+ influx, leading to impaired responses to antigen receptor engagement, including defective activation of phospholipase C?1 and a markedly impaired Ca2+ influx in T cells but not B cells. These observations reveal a role for Mg2+ as an intracellular second messenger coupling cell-surface receptor activation to intracellular effectors and identify MAGT1 as a possible target for novel therapeutics.
- Publication
Nature, 2011, Vol 475, Issue 7357, p471
- ISSN
0028-0836
- Publication type
Academic Journal
- DOI
10.1038/nature10246