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

Summary

Ca²⁺ 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 Ca²⁺ signals. With 300 ms blue light exposure, LOVS1K translocated to Orai1, a plasma membrane Ca²⁺ channel, within seconds, generating a local Ca²⁺ signal on the plasma membrane, and returning to the cytoplasm after tens of seconds. With repeated photoactivation, global Ca²⁺ signals in the cytoplasm were generated to modulate engineered Ca²⁺-inducible proteins. Although Orai1 is typically associated with global store-operated Ca²⁺ entry, we demonstrate that Orai1 can also generate local Ca²⁺ influx on the plasma membrane. Our photoactivation system can be used to generate spatially and temporally precise Ca²⁺ signals and to engineer synthetic proteins that respond to specific Ca²⁺ signals.