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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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Main Authors: Sárkány, Orsolya (Author) , Szőke, Anita (Author) , Pettkó-Szandtner, Aladár (Author) , Kálmán, Eszter Éva (Author) , Brunner, Michael (Author) , Gyöngyösi, Norbert (Author) , Káldi, Krisztina (Author)
Format: Article (Journal)
Language:English
Published: October 2025
In: The FEBS journal
Year: 2025, Volume: 292, Issue: 20, Pages: 5335-5354
ISSN:1742-4658
DOI:10.1111/febs.70122
Online Access: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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Author Notes:Orsolya Sárkány, Anita Szőke, Aladár Pettkó-Szandtner, Eszter Éva Kálmán, Michael Brunner, Norbert Gyöngyösi and Krisztina Káldi
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Summary: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.
Item Description:Online verfügbar: 02. Mai 2025
Gesehen am 29.10.2025
Physical Description:Online Resource
ISSN:1742-4658
DOI:10.1111/febs.70122

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