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Nature 443, 230-233 (20 August 2006) | doi:10.1038/nature05122;

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Orai1 is an essential pore subunit of the CRAC channel

Stimulation of immune cells causes depletion of Ca2|[plus]| from endoplasmic reticulum (ER) stores, thereby triggering sustained Ca2|[plus]| entry through store-operated Ca2|[plus]| release-activated Ca2|[plus]| (CRAC) channels, an essential signal for lymphocyte activation and proliferation. Recent evidence indicates that activation of CRAC current is initiated by STIM proteins, which sense ER Ca2|[plus]| levels through an EF-hand located in the ER lumen and relocalize upon store depletion into puncta closely associated with the plasma membrane.

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