Verde, F. | Search bioRxiv

bioRxiv2021

The Orb6-Sts5 Axis Regulates Stress Granule Formation and Heat Stress Response in Fission Yeast

Cellular response to environmental fluctuations, such as increased temperature, is crucial in promoting cell survival and plays an increasingly recognized role in cancer biology. Important cellular functions altered by heat stress are cell polarization and protein translation. Previous studies have shown that heat stress alters the dynamics of Cdc42, a key regulator of cell polarization in eukaryotes, and promotes RNP granule formation, reprogramming protein translation. The biological mechanisms underlying these vast changes are only partially known. Here, we report that conserved NDR kinase Orb6, a homologue of mammalian STK38, responds to heat stress and regulates heat stress resilience by modulating Cdc42 dynamics and promoting stress granule assembly. Also, we discovered a finely tuned mechanism whereby stress-activated MAP kinase Sty1 negatively regulates Orb6 kinase and Orb6 C-terminal phosphorylation during heat stress. Orb6 inhibition by Sty1 increases the sensitivity of the cell to heat stress in a temperature-specific manner, fostering increased stress resilience and metabolic adaptation. These observations highlight the role of NDR kinase in the process of heat adaptation and thermotolerance during environmental cell exposure to elevated temperatures. Summary statementNuclear Dbf2-related kinase Orb6 inhibition by stress-activated protein kinase Sty1 promotes heat stress resilience in a temperature specific manner.

cell biology↗

bioRxiv2020

Cdc42 GTPase Activating Proteins (GAPs) Maintain Generational Inheritance of Cell Polarity and Cell Shape in Fission Yeast

The highly conserved small GTPase Cdc42 regulates polarized cell growth and morphogenesis from yeast to humans. We previously reported that Cdc42 activation exhibits oscillatory dynamics in Schizosaccharomyces pombe cells. Mathematical modeling suggests that this dynamic behavior enables a variety of symmetric and asymmetric Cdc42 distributions to coexist in cell populations. For individual wild type cells, however, growth follows a stereotypical pattern where Cdc42 distribution is initially asymmetrical in young daughter cells and becomes more symmetrical as cell volume increases, enabling bipolar growth activation. To explore whether different states of Cdc42 activation are possible in a biological context, we examined S. pombe rga4{Delta} mutant cells, lacking the Cdc42 GTPase activating protein (GAP) Rga4. We found that monopolar rga4{Delta} mother cells divide asymmetrically leading to the emergence of both symmetric and asymmetric Cdc42 distributions in rga4{Delta} daughter cells. Using genetic screening approaches to identify mutants that alter the rga4{Delta} phenotype, we tested the predictions of different computational models that reproduce the unequal fate of daughter cells. We found experimentally that the unequal distribution of active Cdc42 GTPase in daughter cells is consistent with an unequal inheritance of another Cdc42 GAP, Rga6, in the two daughter cells. Our findings highlight the crucial role of Cdc42 GAP protein localization in determining the morphological fate of cell progeny and ensuring consistent Cdc42 activation and growth patterns across generations.

cell biology↗