UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony

Abstract

Ubiquitin ligases control the degradation of core clock proteins to govern the speed and resetting properties of the circadian pacemaker. However, few studies have addressed their potential to regulate other cellular events within clock neurons beyond clock protein turnover. Here, we report that the ubiquitin ligase, UBR4/POE, strengthens the central pacemaker by facilitating neuropeptide trafficking in clock neurons and promoting network synchrony. Ubr4-deficient mice are resistant to jetlag, whereas poe knockdown flies are prone to arrhythmicity, behaviors reflective of the reduced axonal trafficking of circadian neuropeptides. At the cellular level, Ubr4 ablation impairs the export of secreted proteins from the Golgi apparatus by reducing the expression of Coronin 7, which is required for budding of Golgi-derived transport vesicles. In summary, UBR4/POE fulfills a conserved and unexpected role in the vesicular trafficking of neuropeptides, a function that has important implications for circadian clock synchrony and circuit-level signal processing.

Efficient strategies based on behavioral and electrophysiological methods for epilepsy-related gene screening in the Drosophila model

“…Due to these factors, spatiotemporal genetic modifications, such as those enabled by the UAS/Gal4 system, can be used to conduct fly research in just a few months ( Kepecs et al, 2002 ; Takai et al, 2020 ; Guerrini et al, 2021 ). The discovery of the Drosophila model is also easy to translate to other vertebrate models ( Hunt et al, 2019 ; Hegazi et al, 2022 ).…”