Work

Novel STIM1‐dependent control of Ca 2+ clearance regulates NFAT activity during T‐cell activation

Year: 2016

Type: article

Abstract: ABSTRACT Antigen presentation to the T‐cell receptor leads to sustained cytosolic Ca 2+ elevation, which is critical for T‐cell activation. We previously showed that in activated T cells, Ca 2+ clearance is inhibited by the end oplasmic reticulum Ca 2+ sensor stromal interacting molecule 1 (STIM1) via association with the plasma membrane Ca 2+ /ATPase 4 (PMCA4) Ca 2+ pump. Having further observed that expression of both proteins is increased in activated T cells, the current study focused on mechanisms regulating both up‐regulation of STIM1 and PMCA4 and assessing how this up‐regulation contributes to control of Ca 2+ clearance. Using a STIM1 promoter luciferase vector, we found that the zinc finger transcription factors early growth response (EGR) 1 and EGR4, but not EGR2 or EGR3, drive luciferase activity. We further found that neither STIM1 nor PMCA4 is up‐regulated when both EGR1 and EGR4 are knocked down using RNA interference. Further, under these conditions, activation‐induced Ca 2+ clearance inhibition was eliminated with little effect on Ca 2+ entry. Finally, we found that nuclear factor of activated T‐cell (NFAT) activity is profoundly attenuated if Ca 2+ clearance is not inhibited by STIM1. These findings reveal a critical role for STIM1‐mediated control of Ca 2+ clearance in NFAT induction during T‐cell activation.—Samakai, E., Hooper, R., Martin, K. A., Shmurak, M., Zhang, Y., Kappes, D. J., Tempera, I., Soboloff, J. Novel STIM1‐dependent control of Ca 2+ clearance regulates NFAT activity during T‐cell activation. FASEB J. 30, 3878–3886 (2016) www.fasebj.org

Source: The FASEB Journal

DOI: 10.1096/fj.201600532r