Hijacking of internal calcium dynamics by intracellularly residing rhodopsins

Rhodopsins are ubiquitous light-driven membrane proteins with diverse functions, including ion transport. Widely distributed, they are also coded in the genomes of giant viruses infecting phytoplankton where their function is not settled. We examined the properties of three type 1 viral channelrhodopsins (VCR1s), and, unexpectedly, found that VCR1s accumulate exclusively intracellularly, and, upon illumination, induced calcium release from intracellular IP₃-dependent stores. In vivo, this light-induced calcium release was sufficient to remote control muscle contraction and behavior in VCR1-expressing tadpoles. VCR1s are the first rhodopsins shown to natively confer light-induced Ca²⁺release, suggesting an original mechanism for reshaping the response to light of virus-infected algae. The ability of VCR1s to photorelease calcium without altering plasma membrane electrical properties marks them as precursors for novel optogenetics tools, with potential applications in basic research and medicine.