Sensing ER Stress

Direct binding of unfolded proteins to a sensor in the endoplasmic reticulum triggers sensor oligomerization and a cellular stress response. The endoplasmic reticulum (ER) is sometimes described as the factory of the eukaryotic cell. Most lipids, glycans, and about a third of the proteome are synthesized in this organelle. As with any modern factory, quality control mechanisms are in place to sort and remove defective products from distribution from the ER. A key regulator of this microeconomy is the unfolded protein response (UPR) signaling pathway. On page 1891 in this issue, Gardner and Walter (1) describe a molecular mechanism by which the sensor protein Ire1 detects and communicates ER stress.

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