Fig. 8: Summary of findings from the current study.
From: The native ORAI channel trio underlies the diversity of Ca2+ signaling events
a Native CRAC channels are constructed of ORAI isoform heteromers (dashed box). Incorporation of ORAI3 and ORAI2 with ORAI1 into hexameric CRAC channels fine-tunes SOCE to gradually match the strength of agonist stimulation. CRAC channels containing ORAI2 or ORAI3 or both will have weaker activity but will more readily activate through preferential interactions with STIM1 at low levels of store depletion. b In wild-type cells, ORAI2 and ORAI3 expand the range of sensitivity of receptor-activated Ca2+ signals to induce differential NFAT isoform nuclear translocation. In their absence, both NFAT1 and NFAT4 are substantially induced in response to low concentrations of agonist. Although native ORAI2 and ORAI3 can mediate SOCE when other ORAI isoforms are absent, they are incapable of supporting NFAT nuclear translocation. Whether ORAI isoform homohexamers exist under native conditions is uncertain. Our data suggest that ORAI3 and ORAI2 isoforms are unlikely to function independently of ORAI1 under native conditions. However, the precise stoichiometry or stoichiometries of native CRAC channels is likely cell type-specific and requires further investigations.
