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Crosstalk Between Ras and Inositol Phosphate Signaling Revealed by Lithium Action on Inositol Monophosphatase in Schizophyllum commune

Summary

This research reveals how two important cellular communication systems interact in fungi, specifically looking at how lithium affects cellular signaling. The findings help explain how lithium, commonly used to treat bipolar disorder, affects cells at a molecular level. The study used a mushroom-forming fungus as a model organism to understand these complex interactions. Impacts on everyday life: – Provides new insights into how lithium medications work in treating mental health conditions – Advances our understanding of fundamental cellular communication processes – Demonstrates how simple organisms can help us understand complex human biology – Could lead to development of more effective treatments for mood disorders – Shows how different signaling systems in cells work together to maintain proper function

Background

Inositol based signaling pathways are among the most complex regulatory networks in eukaryotic cells. The phosphatidylinositol signaling cascade and turnover of inositol phosphates regulate many cellular activities. The mushroom forming basidiomycete Schizophyllum commune has been used to study fungal sexual development, where Ras signaling activation via G-protein-coupled receptors plays a significant role in mating and development.

Objective

To investigate the crosstalk between Ras signaling and inositol phosphate signaling through inositol monophosphatase (IMPase) in S. commune, and examine the effects of lithium inhibition on IMPase activity and inositol phosphate metabolism.

Results

The study revealed that constitutively active Ras1 leads to repression of IMPase transcription. Lithium treatment inhibited IMPase activity and induced significant metabolic changes, leading to increased levels of higher phosphorylated inositol species in wild type cells but not in the Ras1 mutant. Proteome analysis showed changes in cellular processes and signaling pathways affected by lithium treatment.

Conclusion

The research uncovered a previously unknown crosstalk between Ras and inositol phosphate signaling pathways in S. commune. Lithium inhibition of IMPase led to unprecedented accumulation of higher phosphorylated inositol species, an effect that was dependent on normal Ras signaling. This provides new perspectives for understanding lithium’s mechanism of action in cellular signaling.
  • Published in:Advances in Biological Regulation,
  • Study Type:Laboratory Research,
  • Source: 10.1016/j.jbior.2019.01.001
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