The Small Yeast GTPase Rho5 and Its Dimeric GEF Dck1/Lmo1 Respond to Glucose Starvation

Hans-Peter Schmitz,Carolin Sterk,Jürgen Heinisch,Arne Jendretzki

doi:10.3390/ijms19082186

Hans-Peter Schmitz, Carolin Sterk + Show 2 more

Open Access

https://doi.org/10.3390/ijms19082186

Copy DOI

Abstract

Rho5 is a small GTPase of Saccharomyces cerevisiae and a homolog of mammalian Rac1. The latter regulates glucose metabolism and actin cytoskeleton dynamics, and its misregulation causes cancer and a variety of other diseases. In yeast, Rho5 has been implicated in different signal transduction pathways, governing cell wall integrity and the responses to high medium osmolarity and oxidative stress. It has also been proposed to affect mitophagy and apoptosis. Here, we demonstrate that Rho5 rapidly relocates from the plasma membrane to mitochondria upon glucose starvation, mediated by its dimeric GDP/GTP exchange factor (GEF) Dck1/Lmo1. A function in response to glucose availability is also suggested by synthetic genetic phenotypes of a rho5 deletion with gpr1, gpa2, and sch9 null mutants. On the other hand, the role of mammalian Rac1 in regulating the action cytoskeleton does not seem to be strongly conserved in S. cerevisiae Rho5. We propose that Rho5 serves as a central hub in integrating various stress conditions, including a crosstalk with the cAMP/PKA (cyclic AMP activating protein kinase A) and Sch9 branches of glucose signaling pathways.

Highlights

Monomeric G-proteins, frequently referred to as small GTPases, fulfill essential functions as molecular switches in a variety of biological processes in all eukaryotic cells, including signaling cascades, vesicle trafficking, cytoskeletal organization, and cell migration [1,2]
Strains lacking Rho5 showed neither a prominent effect on the low number of actin patches observed in yeast mother cells, nor on the sensitivity towards the actin-polymerization inhibitor Latrunculin A
The finding that actin patch numbers increased threefold in the dck1 deletion as compared to wild-type mother cells, and 30% in the lmo1 deletion, indicates that either the dimeric GTP exchange factor (GEF) Dck1/Lmo1, or Dck1 by itself, may interact with another GTPase which is involved in the organization of the actin cytoskeleton

Summary

Introduction

Monomeric G-proteins, frequently referred to as small GTPases, fulfill essential functions as molecular switches in a variety of biological processes in all eukaryotic cells, including signaling cascades, vesicle trafficking, cytoskeletal organization, and cell migration [1,2]. Rho was first described as a regulator of yeast cell wall integrity (CWI) signaling (Figure 1A) [4,5]. Upon addition of hydrogen peroxide the trimeric complex rapidly relocates from a diffuse and partially patchy cytosolic distribution (Dck1/Lmo; compare Figure 1B) and the plasma membrane (Rho5) to mitochondria, providing a mechanical link to the roles observed in mitophagy and apoptosis [10]. Deletion of RHO5, and of DCK1 or LMO1, led to hyper-resistance towards the cell wall stress agents Calcofluor white and Congo red, supporting the originally proposed link to CWI signaling [4,10]

Methods

Results

Conclusion