Light generation of intracellular Ca2þ signals

Ca2þ signals are highly regulated in a spatiotemporal manner in numerous cellular physiological events. Here we report a genetically engineered blue light-activated Ca2þ channel switch (BACCS), as an optogenetic tool for generating Ca2þ signals. BACCS opens Ca2þ-selective ORAI ion channels in response to light. A BACCS variant, dmBACCS2, combined with Drosophila Orai, elevates the Ca2þ concentration more rapidly, such that Ca2þ 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 Ca2þ. Thus, BACCSs are a useful optogenetic tool for generating temporally various intracellular Ca2þ signals with a large dynamic range, and will be applicable to bot