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

Abstract

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. Lightactivated 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.phototransduction | potassium channel | redox | cryptochrome

CRYPTOCHROME mediates behavioral executive choice in response to UV light

“…1G). Thus, electrophysiological responses to UV light are specifically mediated by light-activated CRY coupled to the membrane via HK redox sensor, consistent with previous findings using blue light (8).…”

“…Light-modulated behaviors are driven by the modulation of membrane excitability in contributing neurons, such as the l-LNvs (5,6,(8)(9)(10)(11). We tested whether similar l-LNv electrophysiological response (firing frequency light on/light off) was observed in response to UV light.…”

“…CRY is expressed in circadian, arousal, and photoreceptor neurons (3,11,28,30), including l-LNvs, which mediate acute arousal behavioral responses to blue light at physiological intensities that transmit the head and eye cuticles (8). We measured the proportion of UV light transmittance through eye and head cuticle tissue using a 365-nm LED light source using procedures described in ref.…”

“…In Drosophila melanogaster, CRY mediates rapid membrane depolarization and increased spontaneous action potential firing rate in the lateral ventral neurons (LNvs), which are involved in arousal and circadian behavioral responses (1-7). Blue-lightactivated CRY couples to membrane depolarization in Drosophila LNv neurons by a redox-based mechanism involving potassium channel heteromultimeric complexes, consisting of the downstream redox sensor cytoplasmic potassium beta (Kvβ), HYPERKINETIC (HK), and ion-conducting voltage-gated potassium alpha (Kvα) ether-a-go-go family subunits (8). Electrical activity in the LNvs contributes to circadian rhythms (9)(10)(11), and, reciprocally, LNv neuronal firing rate is circadian-regulated (1,2,12).…”

Quasimodo mediates daily and acute light effects on Drosophila clock neuron excitability

“…Qsm acts either independently or downstream of Cry and also is able to affect clock protein stability in Qsmnegative neurons by an unknown non-cell-autonomous mechanism (16). Recently Cry has been shown to regulate clock neuron excitability via the redox sensor of the Hyperkinetic voltage-gated potassium (K V )-β subunit (Hk) (18,19), and here we ask if Qsm affects the clock neurons in a similar way.Membrane potential is important for control of circadian behavior, and manipulation of Shaw and the Narrow Abdomen (NA) channels, both of which are expressed and function within clock neurons influence neuronal electrical activity, the circadian clock, and clockcontrolled behavior in both flies (20-22) and mice (23-25). The firing rate is a key component in mammalian circadian rhythmicity and can be regulated by regional and circadian expression of the sodium potassium chloride cotransporter NKCC, which switches the effects of GABA from inhibitory to excitatory across the day (26, 27).…”