TRPM4 regulates calcium oscillations after T cell activation.
TRPM4 has recently been described as a calcium-activated nonselective (CAN) cation channel that mediates membrane depolarization. However, the functional importance of TRPM4 in the context of calcium (Ca2+) signaling and its effect on cellular responses are not known. Here, the molecular inhibition of endogenous TRPM4 in T cells was shown to suppress TRPM4 currents, with a profound influence on receptor-mediated Ca2+ mobilization. Agonist-mediated oscillations in intracellular Ca2+ concentration ([Ca2+]i), which are driven by store-operated Ca2+ influx, were transformed into a sustained elevation in [Ca2+]i. This increase in Ca2+ influx enhanced interleukin-2 production. Thus, TRPM4-mediated depolarization modulates Ca2+ oscillations, with downstream effects on cytokine production in T lymphocytes.
Launay
Pierre
P
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
Cheng
Henrique
H
Srivatsan
Subhashini
S
Penner
Reinhold
R
Fleig
Andrea
A
Kinet
Jean-Pierre
JP
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling; D027682:Cation Transport Proteins / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D047468:Immunoprecipitation; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D051379:Mice; D018408:Patch-Clamp Techniques; D010835:Phytohemagglutinins / Q000494:pharmacology; D034622:RNA Interference; D012964:Sodium / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D050053:TRPM Cation Channels
D015220:Calcium Channels; D027682:Cation Transport Proteins; D007376:Interleukin-2; D010835:Phytohemagglutinins; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C476766:TRPM4 protein, mouse; D012964:Sodium; D002118:Calcium