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Homeostatic control of START through negative feedback between Cln3-Cdk1 and Rim15/Greatwall kinase in budding yeast
Nicolas Talarek1, Elisabeth Gueydon1, Etienne Schwob1
1IGMM, CNRS, University of Montpellier, Montpellier, France.
Elife
|June 11, 2017
Summary
The Rim15-Igo1,2 pathway regulates cell size homeostasis by controlling Whi5 phosphorylation, crucial for cell cycle entry. This pathway
Area of Science:
- Cell biology
- Molecular biology
- Biochemistry
Background:
- Cell size homeostasis is critical for proper cell division.
- G1-cyclin-dependent kinases (CDKs) phosphorylate Whi5/Rb inhibitors, initiating S-phase entry.
- The precise mechanisms regulating cell cycle entry at specific sizes remain unclear.
Purpose of the Study:
- To investigate the role of the Rim15-Igo1,2 pathway in cell size control and cell cycle progression.
- To elucidate how metabolic rewiring influences cell cycle entry.
Main Methods:
- Yeast genetics (gene deletions, overexpression).
- Cell cycle analysis.
- Biochemical assays to assess protein phosphorylation and activity.
Main Results:
- The Rim15-Igo1,2 pathway promotes START by inhibiting PP2ACdc55-mediated dephosphorylation of Whi5.
- RIM15 overexpression reduces cell size; IGO1,2 deletion delays START, especially with low CDK activity.
- Rim15 activity is modulated by metabolic state (fermentation to respiration) and inhibited by Cln3-Cdk1, enabling homeostatic control.
Conclusions:
- The Rim15-Igo1,2 pathway is a key regulator of Whi5 phosphorylation and cell cycle entry.
- This pathway contributes to cell size homeostasis during metabolic transitions.
- Regulation of PP2A by Rim15/Gwl is crucial for integrating metabolic state with cell cycle progression.
Keywords:
PP2A phosphataseRim15/GwlS. cerevisiaeSTART/restriction pointWhi5/Rbcell biologycell cyclecell size homeostasisMore Related Videos
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