Research ArticleCalcium signaling

Differential regulation of Ca2+ influx by ORAI channels mediates enamel mineralization

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Science Signaling  23 Apr 2019:
Vol. 12, Issue 578, eaav4663
DOI: 10.1126/scisignal.aav4663

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Preventing CRAC’d teeth

Store-operated Ca2+ entry (SOCE) through CRAC channels, specifically complexes formed by ORAI Ca2+ channels and STIM Ca2+ sensors, mediates Ca2+ uptake in enamel cells in teeth. Eckstein et al. described a patient with a null mutation in ORAI1 that likely accounted for the defective enamel mineralization in his teeth. In mice, deficiency of ORAI1, but not that of ORAI2, decreased SOCE in enamel cells and resulted in compromised enamel structure. In an enamel cell line, ORAI1 knockdown increased mitochondrial cellular respiration, resulting in altered redox status that increased the efficiency of Ca2+ uptake in the ER. These results indicate that ORAI1 is the major CRAC channel in enamel cells and reveal the mechanisms by which SOCE affects enamel cell function.