Defects in the secretory pathway and high Ca2+ induce multiple P-bodies.
mRNA is sequestered and turned over in cytoplasmic processing bodies (PBs), which are induced by various cellular stresses. Unexpectedly, in Saccharomyces cerevisiae, mutants of the small GTPase Arf1 and various secretory pathway mutants induced a significant increase in PB number, compared with PB induction by starvation or oxidative stress. Exposure of wild-type cells to osmotic stress or high extracellular Ca(2+) mimicked this increase in PB number. Conversely, intracellular Ca(2+)-depletion strongly reduced PB formation in the secretory mutants. In contrast to PB induction through starvation or osmotic stress, PB formation in secretory mutants and by Ca(2+) required the PB components Pat1 and Scd6, and calmodulin, indicating that different stressors act through distinct pathways. Consistent with this hypothesis, when stresses were combined, PB number did not correlate with the strength of the translational block, but rather with the type of stress encountered. Interestingly, independent of the stressor, PBs appear as spheres of approximately 40-100 nm connected to the endoplasmic reticulum (ER), consistent with the idea that translation and silencing/degradation occur in a spatially coordinated manner at the ER. We propose that PB assembly in response to stress occurs at the ER and depends on intracellular signals that regulate PB number.
Biozentrum, Growth and Development, University of Basel, CH-4056 Basel, Switzerland.
Cornelia
C
Kilchert
Julie
J
Weidner
Cristina
C
Prescianotto-Baschong
Anne
A
Spang
D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D022083:Cytoplasmic Structures / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005990:Glycerol / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009997:Osmotic Pressure / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D055571:Secretory Pathway / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects
D002147:Calmodulin; D029701:Saccharomyces cerevisiae Proteins; D005990:Glycerol; D002118:Calcium