Topic: Hyperkinetic

Voltage-gated potassium (Kv) channels couple with cytoplasmic ß-subunits (Kvß) that exhibit aldo-keto reductase (AKR) activity. Kvß subunits typically have exceptionally low catalytic turnover making them slow substrate converters. This poses a conundrum: why would an ion channel be shackled with a subpar enzyme? The AKR activity is crucial in Drosophila sleep regulation in dorsal fan-shaped body neurons (dFBN) where the Kv1 family member, Shaker, is paired with the ß-subunit Hyperkinetic. We show that its low catalytic turnover permits Hyperkinetic to monitor and integrate cumulative oxidativ

Sleep is vital, but its benefits are unknown. One hypothesis posits that sleep is an antioxidant defence mechanism. Indeed, reactive oxygen species (ROS) have been shown to accumulate during prolonged waking, and experimentally increasing the ROS load of the brain induces sleep. In Drosophila melanogaster, a crucial ROS sensor in sleep-promoting dorsal fan-shaped body neurons (dFBNs) is the β-subunit, termed Hyperkinetic (Hk), of the voltage-gated potassium channel Shaker. Oxidation of a stably bound NADPH cofactor causes conformational changes in the channel, which increase dFBN activity. dFB

Recent advances in understanding the biomolecular mechanisms of sleep control in the Drosophila model have implicated mitochondrial ROS as a key cog in the machine. Hyperkinetic, the beta subunit to the potassium channel Shaker, has been shown to act as a conduit translating rising levels of that mitochondrial ROS during waking hours to heightened cell excitability in the sleep-controlling dorsal fan-shaped body-projecting neurons (dFB) in flies. In order to explore the universality of this mechanism, we instigated a parallel study in mice. Hyperkinetic has three homologs in the mammalian geno