Photocontrol of intracellular calcium by a new class of viral rhodopsins : Application to light-mediated restoration of muscle contraction in paralyzed animals

Channelrhodopsins are light-activated ion channels found in microbes. Although their roles often remain enigmatic, they are widely used in optogenetics to photocontrol specific neurons in higher organisms.

Widely distributed in microorganisms, they are also encoded in the genomes of giant viruses infecting phytoplankton, where their function is not established. The Channels team of the Membrane Transporters Group (IBS/MEMBRANE) examined the properties of viral channelrhodopsins type 1 (VCR1s), and demonstrated that VCR1s accumulate exclusively inside cells and, under the effect of light, induces calcium release from IP3-dependent intracellular stores. In vivo, this light-induced calcium release is sufficient to remotely control muscle contraction in tadpoles expressing VCR1 (collaboration with the Institut de Biologie Valrose (iBV), Nice).

This function of VCR1s suggests an original mechanism for remodeling the light response of virus-infected algae. In eukaryotes, calcium is a universal intracellular messenger involved in physiological mechanisms as diverse as hormone secretion, memory, apoptosis, muscle contraction and so on. The ability of VCR1s to photomodulate intracellular calcium without altering the electrical properties of the plasma membrane marks them as precursors of new optogenetic tools, with potential applications in basic research and medicine.

Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins. Ana-Sofia Eria-Oliveira, Mathilde Folacci, Anne Amandine Chassot, Sandrine Fedou, Nadine Thézé, Dmitrii Zabelskii, Alexey Alekseev, Ernst Bamberg, Valentin Gordeliy, Guillaume Sandoz, Michel Vivaudou. Nature Communications (2024) 15:65. doi : 10.1038/s41467-023-44548-6.

Contact : Michel Vivaudou (vivaudou.lab at (IBS/Membrane Transporters Group) & Ana-Sofia Eria-Oliveira (iBV)