Identification of Dck1 and Lmo1 as upstream regulators of the small GTPase Rho5 in Saccharomyces cerevisiae

Autor(en): Schmitz, Hans-Peter 
Jendretzki, Arne
Wittland, Janina
Wiechert, Johanna
Heinisch, Juergen J.
Stichwörter: Biochemistry & Molecular Biology; BUDDING YEAST; CELL-DEATH; EXCHANGE FACTORS; GENE DELETION; MAPK; Microbiology; MITOPHAGY; OXIDATIVE STRESS; PROTEIN-KINASE-C; SHUTTLE VECTORS; SIGNALING PATHWAYS
Erscheinungsdatum: 2015
Herausgeber: WILEY
Journal: MOLECULAR MICROBIOLOGY
Volumen: 96
Ausgabe: 2
Startseite: 306
Seitenende: 324
Zusammenfassung: 
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.
ISSN: 0950382X
DOI: 10.1111/mmi.12937

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