title: The MAP kinase Slt2 is involved in vacuolar function and actin remodeling in Saccharomyces cerevisiae mutants affected by endogenous oxidative stress.
abstract: Oxidative stress causes transient actin cytoskeleton depolarization and also provokes vacuole fragmentation in wild-type cells. Under conditions of oxidative stress induced by hydrogen peroxide, the Slt2 protein is required to repolarize the actin cytoskeleton and to promote vacuole fusion. In this study, we show that grx3 grx4 and grx5 mutants are cellular models of endogenous oxidative stress. This stress is the result of alterations in iron homeostasis that lead to impairment of vacuolar function and also to disorganization of the actin cytoskeleton. Slt2 overexpression suppresses defects in vacuolar function and actin cytoskeleton organization in the grx3 grx4 mutant. Slt2 exerts this effect independently of the intracellular levels of reactive oxygen species (ROS) and of iron homeostasis. The deletion of SLT2 in the grx3 grx4 mutant results in synthetic lethality related to vacuolar function with substantial vacuole fragmentation. The observation that both Vps4 and Vps73 (two proteins related to vacuole sorting) suppress vacuole fragmentation and actin depolarization in the grx3 grx4 slt2 triple mutant strengthens the hypothesis that Slt2 plays a role in vacuole homeostasis related to actin dynamics. Here we show that in sod1, grx5, and grx3 grx4 slt2 mutants, all of which are affected by chronic oxidative stress, the overexpression of Slt2 favors vacuole fusion through a mechanism dependent on an active actin cytoskeleton.
authors: Department de Ciències Mèdiques Bàsiques, Institut de Recerca Biomedica, Universidad de Lleida, Lleida, Spain.
authors: Nuria
authors: N
authors: Pujol-Carrion
authors: Mima I
authors: MI
authors: Petkova
authors: Luis
authors: L
authors: Serrano
authors: Maria Angeles
authors: MA
authors: de la Torre-Ruiz
mesh_terms: D000199:Actins / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000633:toxicity; D050296:Microbial Viability / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018384:Oxidative Stress; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000201:enzymology* / Q000378:metabolism
chemical_list: D000199:Actins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae
references: Mol Biol Cell. 2002 Jul;13(7):2486-501
references: 12134085
references: Redox Rep. 2000;5(5):277-85
references: 11145102
references: EMBO J. 1997 Dec 1;16(23):7196-206
references: 9384596
references: Mol Cell Biol. 1999 Dec;19(12):8180-90
references: 10567543
references: Yeast. 1985 Dec;1(2):139-57
references: 3916861
references: Science. 2003 Mar 14;299(5613):1751-3
references: 12610228
references: J Biol Chem. 2002 Nov 8;277(45):43495-504
references: 12171921
references: J Biol Chem. 2005 Mar 11;280(10):9149-59
references: 15637049
references: Mol Cell Biol. 1991 Dec;11(12):5801-12
references: 1944264
references: Mol Cell Biol. 1992 Jan;12(1):172-82
references: 1729597
references: J Biol Chem. 1999 Sep 24;274(39):27590-6
references: 10488097
references: Genetics. 2011 Aug;188(4):859-70
references: 21625004
references: J Biol Chem. 2007 Oct 19;282(42):30466-75
references: 17726018
references: Microbiol Rev. 1990 Sep;54(3):266-92
references: 2215422
references: Mol Cell Biol. 1988 Nov;8(11):4936-48
references: 3062374
references: FEMS Yeast Res. 2009 Dec;9(8):1196-207
references: 19765090
references: Yeast. 1997 Dec;13(15):1423-35
references: 9434348
references: Biochemistry. 1996 Apr 9;35(14):4403-8
references: 8605189
references: J Biol Chem. 2001 Sep 14;276(37):35133-40
references: 11441010
references: EMBO J. 2002 Mar 15;21(6):1241-7
references: 11889030
references: J Biol Chem. 2006 Jun 30;281(26):17661-9
references: 16648636
references: Mol Biol Cell. 2002 Apr;13(4):1109-21
references: 11950925
references: J Cell Sci. 1999 May;112 ( Pt 9):1325-36
references: 10194411
references: J Biol Chem. 2010 Feb 12;285(7):4298-306
references: 20007700
references: IUBMB Life. 2007 Apr-May;59(4-5):293-8
references: 17505968
references: J Biol Chem. 2004 May 7;279(19):19698-704
references: 14993228
references: Curr Protein Pept Sci. 2010 Dec;11(8):669-79
references: 21235503
references: J Biol Chem. 1989 Sep 25;264(27):16037-45
references: 2674123
references: Mol Aspects Med. 2001 Aug-Oct;22(4-5):217-46
references: 11679167
references: J Biol Chem. 2010 Jun 18;285(25):19521-31
references: 20388713
references: J Cell Biol. 1995 Mar;128(5):779-92
references: 7533169
references: J Biol Chem. 2005 Jan 28;280(4):2529-35
references: 15545276
references: Proc Natl Acad Sci U S A. 1990 May;87(9):3503-7
references: 2139726
references: Biochem Soc Trans. 2009 Feb;37(Pt 1):143-5
references: 19143619
references: J Cell Biol. 2002 Aug 19;158(4):669-79
references: 12177043
references: Microbiol Mol Biol Rev. 2006 Mar;70(1):177-91
references: 16524922
references: Biochim Biophys Acta. 2009 Apr;1793(4):650-63
references: 18786576
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13804-9
references: 9391108
references: Fungal Genet Biol. 2012 Nov;49(11):903-14
references: 22960125
references: Cell Mol Life Sci. 2007 Jun;64(12):1518-30
references: 17415523
references: J Biol Chem. 2010 Apr 2;285(14):10232-42
references: 20139087
references: FEMS Yeast Res. 2011 Dec;11(8):656-9
references: 22093750
references: Appl Environ Microbiol. 2010 Dec;76(23):7826-35
references: 20889785
references: J Cell Sci. 2006 Nov 1;119(Pt 21):4554-64
references: 17074835
references: J Bacteriol. 1999 Jun;181(11):3330-40
references: 10348843
references: J Cell Biol. 1988 Oct;107(4):1369-83
references: 3049619
references: FEBS Lett. 1988 Apr 11;231(1):253-8
references: 3282922
references: J Biol Chem. 2002 May 24;277(21):18914-8
references: 11877447
references: J Biol Chem. 2013 Apr 19;288(16):11366-77
references: 23457300
references: Biochem Biophys Res Commun. 2010 Mar 26;394(1):64-9
references: 20171953
references: J Biol Chem. 1991 Jul 25;266(21):13971-7
references: 1830311
references: Microbiology (Reading). 1994 Dec;140 ( Pt 12):3277-83
references: 7881546
references: J Biol Chem. 2012 Apr 20;287(17):13541-8
references: 22247543
references: Mol Cell Biol. 1993 May;13(5):3076-83
references: 8386320
references: J Cell Biol. 2005 Jan 31;168(3):401-14
references: 15684030
references: Autophagy. 2008 Jan;4(1):5-19
references: 17932463
references: EMBO J. 1996 Jul 1;15(13):3377-84
references: 8670839
references: Mol Microbiol. 1991 Nov;5(11):2845-54
references: 1779770
references: J Cell Biol. 1999 Oct 4;147(1):163-74
references: 10508863