Conserved function of a RasGEF-mediated pathway in the metabolic compensation of the circadian clock
Metabolic compensation of the circadian clock ensures endogenous timing across a broad range of nutrient conditions, enabling organisms to adapt efficiently to recurrent environmental changes, even during nutrient scarcity. In this study, we have identified a novel clock-controlled gene, rasgef (Rat...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
October 2025
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| In: |
The FEBS journal
Year: 2025, Jahrgang: 292, Heft: 20, Pages: 5335-5354 |
| ISSN: | 1742-4658 |
| DOI: | 10.1111/febs.70122 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1111/febs.70122 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1111/febs.70122 
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| Verfasserangaben: | Orsolya Sárkány, Anita Szőke, Aladár Pettkó-Szandtner, Eszter Éva Kálmán, Michael Brunner, Norbert Gyöngyösi and Krisztina Káldi |
| Zusammenfassung: | Metabolic compensation of the circadian clock ensures endogenous timing across a broad range of nutrient conditions, enabling organisms to adapt efficiently to recurrent environmental changes, even during nutrient scarcity. In this study, we have identified a novel clock-controlled gene, rasgef (Rat Sarcoma Guanine Nucleotide Exchange Factor), that plays a crucial role in modulating the circadian clock under starvation conditions in the circadian model organism Neurospora crassa. The gene product, RasGEF—a nucleotide exchange factor for the small G protein RAS2P (Rat Sarcoma 2 Protein)—displays glucose-dependent phosphorylation and localization. We show that deletion of rasgef hinders metabolic compensation of the circadian clock to glucose-depleted conditions and disrupts the rhythmic expression of the output gene ccg2. Furthermore, we demonstrate in osteosarcoma cells that the period of the mammalian clock is also compensated across a wide range of extracellular glucose levels and adaptation of the clock to glucose-starved conditions depends on the RasGEF homolog SOS1 (Son of Sevenless 1) and its downstream signaling component ERK (Extracellular Signal-Regulated Kinase). Our results suggest a conserved role of RasGEF-mediated signaling in the maintenance of circadian rhythm under glucose-limited conditions. |
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| Beschreibung: | Online verfügbar: 02. Mai 2025 Gesehen am 29.10.2025 |
| Beschreibung: | Online Resource |
| ISSN: | 1742-4658 |
| DOI: | 10.1111/febs.70122 |