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Fogle, Keri J.; Baik, Lisa S.; Houl, Jerry H.; Tran, Tri T.; Roberts, Logan; Dahm, Nicole A.; Cao, Yu; Zhou, Ming; Holmes, Todd C.
Proceedings of the National Academy of Sciences - PNAS, 02/2015, Letnik: 112, Številka: 7Journal Article
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.
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