A Synthetic Photoactivated Protein to Generate Local or Global Ca2+ Signals

Summary Ca 2+ signals regulate diverse physiological processes through tightly regulated fluxes varying in location, time, frequency, and amplitude. Here, we developed LOVS1K, a genetically encoded and photoactivated synthetic protein to generate local or global Ca 2+ signals. With 300 ms blue light exposure, LOVS1K translocated to Orai1, a plasma membrane Ca 2+ channel, within seconds, generating a local Ca 2+ signal on the plasma membrane, and returning to the cytoplasm after tens of seconds. With repeated photoactivation, global Ca 2+ signals in the cytoplasm were generated to modulate engineered Ca 2+ -inducible proteins. Although Orai1 is typically associated with global store-operated Ca 2+ entry, we demonstrate that Orai1 can also generate local Ca 2+ influx on the plasma membrane. Our photoactivation system can be used to generate spatially and temporally precise Ca 2+ signals and to engineer synthetic proteins that respond to specific Ca 2+ signals.