title: Identification of Dck1 and Lmo1 as upstream regulators of the small GTPase Rho5 in Saccharomyces cerevisiae.
abstract: The exact function and regulation of the small GTPase Rho5, a putative homolog of mammalian Rac1, in the yeast Saccharomyces cerevisiae have not yet been elucidated. In a genetic screen initially designed to identify novel regulators of cell wall integrity signaling, we identified the homologs of mammalian DOCK1 (Dck1) and ELMO (Lmo1) as upstream components which regulate Rho5. Deletion mutants in any of the encoding genes (DCK1, LMO1, RHO5) showed hyper-resistance to cell wall stress agents, demonstrating a function in cell wall integrity signaling. Live-cell fluorescence microscopy showed that Dck1, Lmo1 and Rho5 quickly relocate to mitochondria under oxidative stress and cell viability assays indicate a role of Dck1/Lmo1/Rho5 signaling in triggering cell death as a response to hydrogen peroxide treatment. A regulatory role in autophagy/mitophagy is suggested by the colocalization of Rho5 with autophagic markers and the decreased mitochondrial turnover observed in dck1, lmo1 and rho5 deletion mutants. Rho5 activation may thus serve as a central hub for the integration of different signaling pathways.
authors.affiliation: Faculty of Biology/Chemistry, Department of Genetics Barbarastr. 11, University of Osnabrueck, Osnabrueck, D-49076, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Schmitz
authors.forename: Arne
authors.initials: A
authors.lastname: Jendretzki
authors.forename: Janina
authors.initials: J
authors.lastname: Wittland
authors.forename: Johanna
authors.initials: J
authors.lastname: Wiechert
authors.forename: Jürgen J
authors.initials: JJ
authors.lastname: Heinisch
mesh_terms: D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000604224:DCK1 protein, S cerevisiae; D047908:Intracellular Signaling Peptides and Proteins; C000604225:Lmo1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C474618:RHO5 protein, S cerevisiae; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins