title: Diverse protective roles of the actin cytoskeleton during oxidative stress.
abstract: Actin oxidation is known to result in changes in cytoskeleton organization and dynamics. Actin oxidation is clinically relevant since it occurs in the erythrocytes of sickle cell patients and may be the direct cause of the lack of morphological plasticity observed in irreversibly sickled red blood cells (ISCs). During episodes of crisis, ISCs accumulate C284-C373 intramolecularly disulfide bonded actin, which reduces actin filament dynamics. Actin cysteines 284 and 373 (285 and 374 in yeast) are conserved, suggesting that they play an important functional role. We have been investigating the physiological roles of these cysteines using the model eukaryote Saccharomyces cerevisiae in response to oxidative stress load. During acute oxidative stress, all of the F-actin in wild-type cells collapses into a few puncta that we call oxidation-induced actin bodies (OABs). In contrast, during acute oxidative stress the actin cytoskeleton in Cys-to-Ala actin mutants remains polarized longer, OABs are slower to form, and the cells recover more slowly than wild-type cells, suggesting that the OABs play a protective role. Live cell imaging revealed that OABs are large, immobile structures that contain actin-binding proteins and that can form by the fusion of actin cortical patches. We propose that actin's C285 and C374 may help to protect the cell from oxidative stress arising from normal oxidative metabolism and contribute to the cell's general adaptive response to oxidative stress.
authors.affiliation: Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse 13210, New York, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Farah
authors.forename: Vladimir
authors.initials: V
authors.lastname: Sirotkin
authors.forename: Brian
authors.initials: B
authors.lastname: Haarer
authors.forename: David
authors.initials: D
authors.lastname: Kakhniashvili
authors.forename: David C
authors.initials: DC
authors.lastname: Amberg
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D053778:Thiazolidines; D003545:Cysteine; C037068:latrunculin B