Functional Conservation of the Small GTPase Rho5/Rac1—A Tale of Yeast and Men

Bischof, Linnet; Schweitzer, Franziska; Heinisch, Jürgen J.

doi:10.3390/cells13060472

Cited by 3 publications

References 137 publications

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The Small GTPase Rho5 – Yet Another Player in Yeast Glucose Signaling

Schweitzer,

Bischof,

Walter

et al. 2024

Preprint

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The small GTPase Rho5 has been shown to be involved in regulating the Bakers yeast response to stress on the cell wall, high medium osmolarity, and reactive oxygen species. These stress condi-tions trigger a rapid translocation of Rho5 and its dimeric GDP/GTP exchange factor (GEF) to the mitochondrial surface, which was also observed upon glucose starvation. We here show that rho5 deletions affect carbohydrate metabolism both at the transcriptomic and the proteomic level, in addition to cell wall and mitochondrial composition. Epistasis analyses with deletion mutants in components of the three major yeast glucose signaling pathways indicate a primary role of Rho5 upstream of the Ras2 GTPase in cAMP-mediated protein kinase A signaling. We also observed an inhibitory role of Rho5 on respiratory capacity, which may be explained by its role in mitophagy.

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The Small GTPase Rho5 – Yet Another Player in Yeast Glucose Signaling

Schweitzer,

Bischof,

Walter

et al. 2024

Preprint

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Oxidative stress response mediated by the yeast Rho5 GTPase depends on the proper spatiotemporal distribution of its dimeric GEF

Bischof,

Heinisch

2024

Preprint

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The small GTPase Rho5 acts as a central hub to mediate the yeast’s response to adverse environmental conditions, including oxidative stress, with the concomitant induction of mitophagy and apoptosis. A proper cellular stress response has been correlated with the rapid translocation of the GTPase to the mitochondria, which depends on its activating dimeric GDP/GTP exchange factor (GEF). Here, the small ALFA tag was attached to Rho5 or the GEF subunits Dck1 and Lmo1 to efficiently trap the functional fusion proteins to specific cellular membranes, i.e. the plasma membrane, the mitochon-drial outer membrane, or the nuclear membrane,viafusions of integral membrane proteins residing in these compartments with an ALFA nanobody. The trapped components were subjected to life-cell fluorescence microscopy in combination with GFP fusions of the GTPase or its GEF subunits to investigate their interactionin vivo. We found that the dimeric GEF tends to auto-assemble and form stable dimers independent of its intracellular localization. On the other hand, GFP-Rho5 does not stably colocalize with the trapped GEF, attributed to its transient interaction. Phenotypic analyses of strains with the misslocalized proteins indicate that for a proper oxidative stress response Lmo1 needs to associate with the plasma membrane. In contrast, Rho5 only exerts its role at the mitochondrial surface when it is there in its active conformation. These data underline the importance of the proper spatio-temporal distribution of Rho5-GTP during oxidative stress response.

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