Document Type
Article
Publication Date
2-2016
Abstract
Calcium and magnesium ions have been implicated in T lymphocyte proliferation in response to antigen recognition. Specifically, it is believed that calcium and magnesium elevations in the cytoplasm are necessary for efficient T cell proliferation. Research over the past two decades has focused on identifying the plasma membrane ion channels responsible for governing Ca2+ influx in lymphocytes and Orai-STIM, Kv1.3 and KCa3.1 channels were shown to be crucial for persistent calcium mobilization. Pharmacologic or genetic suppression of calcium influx gives rise to lymphoproliferative defects. In addition to Ca2+, several studies have demonstrated that Mg2+ influx positively regulates proliferation. TRPM7 is a channel-kinase highly expressed in T cells and reported to conduct both Ca2+ and Mg2+. TRPM7 channels give rise to outwardly rectifying currents inhibited by cytosolic Mg2+. TRPM7 protein appears to be necessary for murine thymocyte development, while small reductions in splenic T lymphocyte numbers were observed in TRPM7-deleted mice. Deletion of TRPM7 in a chicken B cell line resulted in severe proliferation defects. In this work we examine the role of TRPM7 kinase in T-cell blastogenesis and proliferation using a recently reported kinase-dead mutant mouse (Kaitsuka et al, Sci. Rep. 2014). Our goal was to compare the effects of extracellular Ca2+/Mg2+ between wildtype and kinase-dead mutant mouse splenic T cells stimulated with PMA/ionomycin. Increasing Ca2+ or Mg2+ stimulated proliferation in both wildtype and kinase-dead mouse lymphocytes but with significant differences. Using a Coulter counter we also measured the diameters of resting and activated T cells in response to changes in external Ca2+/Mg2+. The differences between WT and mutant T cell blastogenesis and proliferation parameters are discussed in the context of controversies regarding the role of TRPM7 channel and kinase function in cellular Mg2+ homeostasis.
Repository Citation
Beesetty, P.,
Matsushita, M.,
& Kozak, J. A.
(2016). Mitogenic Activation and Proliferation of T Lymphocytes in TRPM7 Kinase-Dead Mutant Mice. Biophysical Journal, 110 (3), 605A, Supplement 1.
https://corescholar.libraries.wright.edu/ncbp/1150
DOI
10.1016/j.bpj.2015.11.3233
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