Second messenger role for Mg^sup 2+^ revealed by human T-cell immunodeficiency

The magnesium ion, Mg^sup 2+^, 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 Ca^sup 2+^ does) is unknown. Here we identify mutations in the magnesium transporter gene, MAGT1, in...

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Bibliographic Details
Published in:Nature (London) 2011-07, Vol.475 (7357), p.471
Main Authors: Li, Feng-Yen, 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
Format: Article
Language:English
Subjects:
DNA methylation
Human subjects
Kinases
Lymphocytes
Magnesium
Mutation
Viral infections
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Summary:The magnesium ion, Mg^sup 2+^, 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 Ca^sup 2+^ 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 Mg^sup 2+^ influx is induced by antigen receptor stimulation in normal T cells and by growth factor stimulation in non-lymphoid cells. MAGT1 deficiency abrogates the Mg^sup 2+^ influx, leading to impaired responses to antigen receptor engagement, including defective activation of phospholipase Cγ1 and a markedly impaired Ca^sup 2+^ influx in T cells but not B cells. These observations reveal a role for Mg^sup 2+^ as an intracellular second messenger coupling cell-surface receptor activation to intracellular effectors and identify MAGT1 as a possible target for novel therapeutics. [PUBLICATION ABSTRACT]
ISSN:0028-0836
1476-4687