| Title: | Multiple signaling pathways regulate yeast cell death during the response to mating pheromones |
| Author(s): | Zhang NN; Dudgeon DD; Paliwal S; Levchenko A; Grote E; Cunningham KW; |
| Address: | "Department of Biology and Whitaker Institute for Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA" |
| ISSN/ISBN: | 1059-1524 (Print) 1059-1524 (Linking) |
| Abstract: | "Mating pheromones promote cellular differentiation and fusion of yeast cells with those of the opposite mating type. In the absence of a suitable partner, high concentrations of mating pheromones induced rapid cell death in approximately 25% of the population of clonal cultures independent of cell age. Rapid cell death required Fig1, a transmembrane protein homologous to PMP-22/EMP/MP20/Claudin proteins, but did not require its Ca2+ influx activity. Rapid cell death also required cell wall degradation, which was inhibited in some surviving cells by the activation of a negative feedback loop involving the MAP kinase Slt2/Mpk1. Mutants lacking Slt2/Mpk1 or its upstream regulators also underwent a second slower wave of cell death that was independent of Fig1 and dependent on much lower concentrations of pheromones. A third wave of cell death that was independent of Fig1 and Slt2/Mpk1 was observed in mutants and conditions that eliminate calcineurin signaling. All three waves of cell death appeared independent of the caspase-like protein Mca1 and lacked certain 'hallmarks' of apoptosis. Though all three waves of cell death were preceded by accumulation of reactive oxygen species, mitochondrial respiration was only required for the slowest wave in calcineurin-deficient cells. These findings suggest that yeast cells can die by necrosis-like mechanisms during the response to mating pheromones if essential response pathways are lacking or if mating is attempted in the absence of a partner" |
| Keywords: | "Biopolymers/metabolism Calcineurin/metabolism Calcium/metabolism Cell Death/drug effects Cell Wall/metabolism Chromatin/metabolism Mating Factor Models, Biological Peptides/*pharmacology Pheromones/*pharmacology Reactive Oxygen Species/metabolism Saccharo;" |
| Notes: | "MedlineZhang, Nan-Nan Dudgeon, Drew D Paliwal, Saurabh Levchenko, Andre Grote, Eric Cunningham, Kyle W eng R01 GM053082/GM/NIGMS NIH HHS/ GM072024/GM/NIGMS NIH HHS/ U54 RR020839/RR/NCRR NIH HHS/ GM073038/GM/NIGMS NIH HHS/ R01 GM072024/GM/NIGMS NIH HHS/ GM053082/GM/NIGMS NIH HHS/ RR020839/RR/NCRR NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2006/06/02 Mol Biol Cell. 2006 Aug; 17(8):3409-22. doi: 10.1091/mbc.e06-03-0177. Epub 2006 May 31" |
