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Identification of D ck1 and L mo1 as upstream regulators of the small GTP ase R ho5 in S accharomyces cerevisiae
Author(s) -
Schmitz HansPeter,
Jendretzki Arne,
Wittland Janina,
Wiechert Johanna,
Heinisch Jürgen J.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12937
Subject(s) - biology , microbiology and biotechnology , saccharomyces cerevisiae , autophagy , mitophagy , signal transduction , mitochondrion , gtpase , mutant , tor signaling , rac gtp binding proteins , cdc42 , small gtpase , cell , rac1 , yeast , genetics , gene , apoptosis
Summary The exact function and regulation of the small GTP ase Rho5 , a putative homolog of mammalian Rac1 , in the yeast S accharomyces 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 ( DCK 1 , LMO 1 , RHO 5 ) 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.