Combining different ion-selective channelrhodopsins to control water flux by light

Water transport through water channels, aquaporins (AQPs), is vital for many physiological processes including epithelial fluid secretion, cell migration and adipocyte metabolism. Consequently, modulation of water transport poses significant therapeutic potential in edema, cancer, obesity, brain injury, glaucoma etc. Water flux through AQPs is driven by the osmotic gradient that results from concentration differences of small molecules or ions. Here, we developed a novel optogenetic toolkit that combines the light-gated anion channel Gt ACR1 either with the light-gated K + channel KCR1 or the new NCR1 with high Na + permeability, to manipulate water transport in Xenopus oocytes non-invasively. Water efflux through AQP was achieved by inducing K + and Cl − efflux through light-gated Hc KCR1 and Gt ACR1, respectively. Contrarily, when Gt ACR1 was co-expressed with NCR1, a final inward movement of Na + and Cl − was triggered, and an osmotic gradient was formed to drive water influx through AQP1. In sum, we demonstrated a novel strategy to manipulate water movement into and out of Xenopus oocytes non-invasively through light. These findings provide a new avenue to interfere with water homeostasis as a means to study related biological phenomena across cell types and organisms.