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  • 1
    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
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  • 2
    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
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  • 3
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 144 (1939), S. 944-944 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE mathematical methods1 devised to deal with the analysis and distribution of human ability and temperament2 can be fruitfully applied to problems of isometric and allometric growth3 and to those of physical anthropology4. A ...
    Type of Medium: Electronic Resource
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  • 4
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    American Society of Hematology (ASH)
    In: Blood
    Publication Date: 2018-06-29
    Description: T-cell chronic active Epstein-Barr virus (CAEBV) is a rare disease in which EBV is present predominantly in T cells that infiltrate the tissues; patients have high levels of EBV in the blood. If untreated, patients often develop liver failure, hemophagocytic lymphohistiocytosis, coronary artery aneurysms, EBV infiltrating T cells impairing organ function, or T-cell lymphomas refractory to treatment. At present, hematopoietic stem-cell transplantation is the only curative therapy, and it is critical to make a proper diagnosis and initiate transplantation before the disease progresses to an irreversible stage. Specific medications such as high-dose systemic corticosteroids or ganciclovir combined with either histone deacetylase inhibitors or bortezomib may temporarily reduce systemic toxicity associated with T-cell CAEBV and allow the patient time to receive a transplant. Relapses of the disease after transplantation have also occurred, and the use of donor-derived virus-specific T cells may help to treat these relapses.
    Keywords: How I Treat, Free Research Articles, Lymphoid Neoplasia
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron Letters 9 (1968), S. 4823-4826 
    ISSN: 0040-4039
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Tetrahedron Letters 9 (1968), S. 4823-4826 
    ISSN: 0040-4039
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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