title: Glutaredoxins Grx4 and Grx3 of Saccharomyces cerevisiae play a role in actin dynamics through their Trx domains, which contributes to oxidative stress resistance.
abstract: Grx3 and Grx4 are two monothiol glutaredoxins of Saccharomyces cerevisiae that have previously been characterized as regulators of Aft1 localization and therefore of iron homeostasis. In this study, we present data showing that both Grx3 and Grx4 have new roles in actin cytoskeleton remodeling and in cellular defenses against oxidative stress caused by reactive oxygen species (ROS) accumulation. The Grx4 protein plays a unique role in the maintenance of actin cable integrity, which is independent of its role in the transcriptional regulation of Aft1. Grx3 plays an additive and redundant role, in combination with Grx4, in the organization of the actin cytoskeleton, both under normal conditions and in response to external oxidative stress. Each Grx3 and Grx4 protein contains a thioredoxin domain sequence (Trx), followed by a glutaredoxin domain (Grx). We performed functional analyses of each of the two domains and characterized different functions for them. Each of the two Grx domains plays a role in ROS detoxification and cell viability. However, the Trx domain of each Grx4 and Grx3 protein acts independently of its respective Grx domain in a novel function that involves the polarization of the actin cytoskeleton, which also determines cell resistance against oxidative conditions. Finally, we present experimental evidence demonstrating that Grx4 behaves as an antioxidant protein increasing cell survival under conditions of oxidative stress.
authors.affiliation: Departamento de Ciencias Médicas Básicas-IRBLleida, Facultad de Medicina, Universidad de Lleida, C/Montserrat Roig no. 2, 25008 Lleida, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Pujol-Carrion
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: de la Torre-Ruiz
mesh_terms: D000199:Actins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D054477:Glutaredoxins / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects; D018384:Oxidative Stress; D010088:Oxidoreductases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D054477:Glutaredoxins; C516012:Grx4 protein, S cerevisiae; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C545181:Grx3 protein, S cerevisiae; D010088:Oxidoreductases