Light generation of intracellular Ca 2+ signals by a genetically encoded protein BACCS

Ca 2+ signals are highly regulated in a spatiotemporal manner in numerous cellular physiological events. Here we report a genetically engineered blue light-activated Ca 2+ channel switch (BACCS), as an optogenetic tool for generating Ca 2+ signals. BACCS opens Ca 2+ -selective ORAI ion channels in response to light. A BACCS variant, dmBACCS2, combined with Drosophila Orai, elevates the Ca 2+ concentration more rapidly, such that Ca 2+ elevation in mammalian cells is observed within 1 s on light exposure. Using BACCSs, we successfully control cellular events including NFAT-mediated gene expression. In the mouse olfactory system, BACCS mediates light-dependent electrophysiological responses. Furthermore, we generate BACCS mutants, which exhibit fast and slow recovery of intracellular Ca 2+ . Thus, BACCSs are a useful optogenetic tool for generating temporally various intracellular Ca 2+ signals with a large dynamic range, and will be applicable to both in vitro and in vivo studies.