Cohen N~Schuldiner M, 2017

Pubmed ID 28794014
Title Iron affects Ire1 clustering propensity and the amplitude of endoplasmic reticulum stress signaling.
Authors Nir Cohen, Michal Breker, Anush Bakunts, Kristina Pesek, Ainara Chas, Josepmaria Argemí, Andrea Orsi, Lihi Gal, Silvia Chuartzman, Yoav Wigelman, Felix Jonas, Peter Walter, Robert Ernst, Tomás Aragón, Eelco van Anken, Maya Schuldiner
Abstract The unfolded protein response (UPR) allows cells to adjust secretory pathway capacity according to need. Ire1, the endoplasmic reticulum (ER) stress sensor and central activator of the UPR is conserved from the budding yeast Saccharomyces cerevisiae to humans. Under ER stress conditions, Ire1 clusters into foci that enable optimal UPR activation. To discover factors that affect Ire1 clustering, we performed a high-content screen using a whole-genome yeast mutant library expressing Ire1-mCherry. We imaged the strains following UPR induction and found 154 strains that displayed alterations in Ire1 clustering. The hits were enriched for iron and heme effectors and binding proteins. By performing pharmacological depletion and repletion, we confirmed that iron (Fe3+) affects UPR activation in both yeast and human cells. We suggest that Ire1 clustering propensity depends on membrane composition, which is governed by heme-dependent biosynthesis of sterols. Our findings highlight the diverse cellular functions that feed into the UPR and emphasize the cross-talk between organelles required to concertedly maintain homeostasis.
Citation J. Cell. Sci. 2017; 130:3222-3233
Notes I think this paper warrants addition of a new phenotype: UPR activation or protein/peptide clustering


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Papers Phenotype Conditions Collection Tested mutants Data Details
Cohen N~Schuldiner M, 2017 protein aggregates (Ire1) DTT (1,4-dithiothreitol [2mM]) hom ~4,757 Discrete

Curation history

Sept. 20, 2017 Tested strains to request.
Sept. 20, 2017 Data to load.