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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany
ORAI CHANNEL-DEPENDENT CALCIUM MICRODOMAINS AT THE IMMUNOLOGICAL SYNAPSE ARE IMPORTANT FOR T-CELL SIGNALING
Abstract number: O113
Quintana1 A., Pasche2 M., *Junker1 C., Al-Ansary1 D., Kummerow1 C., Nunez3 L., Villalobos3 C., Becherer2 U., Rettig2 J., Niemeyer1 B., *Hoth1 M.
ORAI channels are calcium channels which are activated following depletion of intracellular calcium stores. Calcium entry through ORAI channels is required for physiological T cell function. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T cell activation. Cell polarization enables restriction of signaling into microdomains, however, it is not known whether calcium microdomains exist at the IS and whether they contribute to T cell signaling. We report the existence of calcium microdomains at the IS using total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signals are low and heterogeneous following IS formation. This is achieved by localizing mitochondria next to ORAI channels and by distributing plasma membrane calcium-ATPases (PMCA) into areas beneath mitochondria. This nano-scale distribution of the different transporters at the IS minimizes calcium microdomain-dependent ORAI inactivation and local calcium export through PMCA, but maximizes calcium import into the cytosol. Therefore, the formation of the IS guarantees that calcium influx through ORAI channels is increased whereas calcium clearance by PMCA is decreased locally. We show that this mechanism enhances global calcium signals, sustains NFAT activity and induces a more efficient T-cell activation.
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Acta Physiologica 2011; Volume 201, Supplement 682 :O113