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10.1038/s41598-018-21004-w

http://scihub22266oqcxt.onion/10.1038/s41598-018-21004-w
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suck abstract from ncbi


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pmid29445164
      Sci+Rep 2018 ; 8 (1 ): 3023
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  • Inactivation of TRPM7 kinase in mice results in enlarged spleens, reduced T-cell proliferation and diminished store-operated calcium entry #MMPMID29445164
  • Beesetty P ; Wieczerzak KB ; Gibson JN ; Kaitsuka T ; Luu CT ; Matsushita M ; Kozak JA
  • Sci Rep 2018[Feb]; 8 (1 ): 3023 PMID29445164 show ga
  • T lymphocytes enlarge (blast) and proliferate in response to antigens in a multistep program that involves obligatory cytosolic calcium elevations. Store-operated calcium entry (SOCE) pathway is the primary source of Ca(2+) in these cells. Here, we describe a novel modulator of blastogenesis, proliferation and SOCE: the TRPM7 channel kinase. TRPM7 kinase-dead (KD) K1646R knock-in mice exhibited splenomegaly and impaired blastogenic responses elicited by PMA/ionomycin or anti-CD3/CD28 antibodies. Splenic T-cell proliferation in vitro was weaker in the mutant compared to wildtype littermates. TRPM7 current magnitudes in WT and KD mouse T cells were, however, similar. We tested the dependence of T-cell proliferation on external Ca(2+) and Mg(2+) concentrations. At a fixed [Mg(2+)(o)] of ~0.4?mM, Ca(2+)(o) stimulated proliferation with a steep concentration dependence and vice versa, at a fixed [Ca(2+)(o)] of ~0.4?mM, Mg(2+)(o) positively regulated proliferation but with a shallower dependence. Proliferation was significantly lower in KD mouse than in wildtype at all Ca(2+) and Mg(2+) concentrations. Ca(2+) elevations elicited by anti-CD3 antibody were diminished in KD mutant T cells and SOCE measured in activated KD splenocytes was reduced. These results demonstrate that a functional TRPM7 kinase supports robust SOCE, blastogenesis and proliferation, whereas its inactivation suppresses these cellular events.
  • |Animals [MESH]
  • |Calcium Channels/metabolism [MESH]
  • |Calcium Signaling/physiology [MESH]
  • |Calcium/*metabolism [MESH]
  • |Cell Proliferation/physiology [MESH]
  • |Gene Knock-In Techniques/methods [MESH]
  • |Lymphocyte Activation/physiology [MESH]
  • |Magnesium/metabolism [MESH]
  • |Mice [MESH]
  • |Mice, Inbred C57BL [MESH]
  • |Spleen/pathology [MESH]
  • |Splenomegaly/metabolism [MESH]
  • |Stromal Interaction Molecule 1/metabolism [MESH]
  • |T-Lymphocytes/metabolism/physiology [MESH]


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