Details

Autor(en) / Beteiligte

• 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

Titel

Second messenger role for Mg2+ revealed by human T-cell immunodeficiency

Ist Teil von

• Nature (London), 2011-07, Vol.475 (7357), p.471-476

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Psychology and Behavioral Sciences Collection

Beschreibungen/Notizen

• The magnesium ion, Mg(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(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(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(2+) influx, leading to impaired responses to antigen receptor engagement, including defective activation of phospholipase Cγ1 and a markedly impaired Ca(2+) influx in T cells but not B cells. These observations reveal a role for Mg(2+) as an intracellular second messenger coupling cell-surface receptor activation to intracellular effectors and identify MAGT1 as a possible target for novel therapeutics.