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  • 1
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    Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-07-13
    Description: The magnesium transporter 1 (MAGT1) is a critical regulator of basal intracellular free magnesium (Mg(2+)) concentrations. Individuals with genetic deficiencies in MAGT1 have high levels of Epstein-Barr virus (EBV) and a predisposition to lymphoma. We show that decreased intracellular free Mg(2+) causes defective expression of the natural killer activating receptor NKG2D in natural killer (NK) and CD8(+) T cells and impairs cytolytic responses against EBV. Notably, magnesium supplementation in MAGT1-deficient patients restores intracellular free Mg(2+) and NKG2D while concurrently reducing EBV-infected cells in vivo, demonstrating a link between NKG2D cytolytic activity and EBV antiviral immunity in humans. Moreover, these findings reveal a specific molecular function of free basal intracellular Mg(2+) in eukaryotic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894782/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894782/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chaigne-Delalande, Benjamin -- Li, Feng-Yen -- O'Connor, Geraldine M -- Lukacs, Marshall J -- Jiang, Ping -- Zheng, Lixin -- Shatzer, Amber -- Biancalana, Matthew -- Pittaluga, Stefania -- Matthews, Helen F -- Jancel, Timothy J -- Bleesing, Jack J -- Marsh, Rebecca A -- Kuijpers, Taco W -- Nichols, Kim E -- Lucas, Carrie L -- Nagpal, Sunil -- Mehmet, Huseyin -- Su, Helen C -- Cohen, Jeffrey I -- Uzel, Gulbu -- Lenardo, Michael J -- T32 GM007618/GM/NIGMS NIH HHS/ -- ZIA AI001187-01/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2013 Jul 12;341(6142):186-91. doi: 10.1126/science.1240094.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Development of the Immune System Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23846901" target="_blank"〉PubMed〈/a〉
    Keywords: CD8-Positive T-Lymphocytes/*immunology ; Cation Transport Proteins/genetics/metabolism ; *Cytotoxicity, Immunologic ; Epstein-Barr Virus Infections/*immunology ; Humans ; Killer Cells, Natural/*immunology ; Magnesium/*immunology ; Magnesium Deficiency/*immunology ; NK Cell Lectin-Like Receptor Subfamily K/genetics/*metabolism ; X-Linked Combined Immunodeficiency Diseases/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Second messenger role for Mg2+ revealed by human T-cell immunodeficiency (2011)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2011-07-29
    Description: 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 Cgamma1 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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159560/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159560/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- ZIA AI000769-14/Intramural NIH HHS/ -- ZIA AI000769-15/Intramural NIH HHS/ -- England -- Nature. 2011 Jul 27;475(7357):471-6. doi: 10.1038/nature10246.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Development Section, Lymphocyte Molecular Genetics Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21796205" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/immunology ; Cation Transport Proteins/genetics ; Female ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Magnesium/*immunology ; Male ; Phospholipase C gamma/genetics/metabolism ; Second Messenger Systems/*immunology ; T-Lymphocytes/*immunology ; T-Lymphocytopenia, Idiopathic CD4-Positive/genetics/*immunology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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