Journal
EMBO JOURNAL
Volume 30, Issue 19, Pages 3895-3912Publisher
WILEY
DOI: 10.1038/emboj.2011.289
Keywords
calcium signals; immunological synapse; mitochondria; ORAI channels; PMCA
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Funding
- Deutsche Forschungsgemeinschaft [SFB 530, A3, SFB 894, A1]
- Graduate College [SFB 894, KR 3430/1-1, A2]
- HOMFOR [SFB 530, C12]
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Cell polarization enables restriction of signalling into microdomains. Polarization of lymphocytes following formation of a mature immunological synapse (IS) is essential for calcium-dependent T-cell activation. Here, we analyse calcium microdomains at the IS with total internal reflection fluorescence microscopy. We find that the subplasmalemmal calcium signal following IS formation is sufficiently low to prevent calcium-dependent inactivation of ORAI channels. This is achieved by localizing mitochondria close to ORAI channels. Furthermore, we find that plasma membrane calcium ATPases (PMCAs) are re-distributed into areas beneath mitochondria, which prevented PMCA up-modulation and decreased calcium export locally. This nano-scale distribution-only induced following IS formation-maximizes the efficiency of calcium influx through ORAI channels while it decreases calcium clearance by PMCA, resulting in a more sustained NFAT activity and subsequent activation of T cells. The EMBO Journal (2011) 30, 3895-3912. doi:10.1038/emboj.2011.289; Published online 16 August 2011
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