CRYPTOCHROME-mediated phototransduction by modulation of the potassium ion channel β-subunit redox sensor

Significance CRYPTOCHROMES (CRYs) are blue light photoreceptors that mediate phototransduction in brain arousal neurons, as well as circadian light entrainment in Drosophila fruit flies. We describe how light-activated Drosophila CRY couples to membrane depolarization and increased action potential firing rate in large ventral lateral arousal neurons. Pharmacological treatments that specifically disrupt the CRY redox-sensitive flavin chromophore or block voltage-gated K ⁺ channels abolish the light response. Correspondingly, we find that the Kvβ channel subunit Hyperkinetic with a well conserved redox sensor domain links light-evoked redox changes in CRY to rapid changes in membrane electrical potential. Blue light activation of the photoreceptor CRYPTOCHROME (CRY) evokes rapid depolarization and increased action potential firing in a subset of circadian and arousal neurons in Drosophila melanogaster . Here we show that acute arousal behavioral responses to blue light significantly differ in mutants lacking CRY, as well as mutants with disrupted opsin-based phototransduction. Light-activated CRY couples to membrane depolarization via a well conserved redox sensor of the voltage-gated potassium (K ⁺) channel β-subunit (Kvβ) Hyperkinetic (Hk). The neuronal light response is almost completely absent in hk ⁻/⁻ mutants, but is functionally rescued by genetically targeted neuronal expression of WT Hk, but not by Hk point mutations that disable Hk redox sensor function. Multiple K ⁺ channel α-subunits that coassemble with Hk, including Shaker, Ether-a-go-go, and Ether-a-go-go–related gene, are ion conducting channels for CRY/Hk-coupled light response. Light activation of CRY is transduced to membrane depolarization, increased firing rate, and acute behavioral responses by the Kvβ subunit redox sensor.