Article

Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response

Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 11/2009; 187(4):525-36. DOI: 10.1083/jcb.200907074
Source: PubMed

ABSTRACT

Cells constantly adjust the sizes and shapes of their organelles according to need. In this study, we examine endoplasmic reticulum (ER) membrane expansion during the unfolded protein response (UPR) in the yeast Saccharomyces cerevisiae. We find that membrane expansion occurs through the generation of ER sheets, requires UPR signaling, and is driven by lipid biosynthesis. Uncoupling ER size control and the UPR reveals that membrane expansion alleviates ER stress independently of an increase in ER chaperone levels. Converting the sheets of the expanded ER into tubules by reticulon overexpression does not affect the ability of cells to cope with ER stress, showing that ER size rather than shape is the key factor. Thus, increasing ER size through membrane synthesis is an integral yet distinct part of the cellular program to overcome ER stress.

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    • "Notable among ER-shaping proteins are reticulons, proteins that insert hairpin-like transmembrane domains into the cytosolic ER membrane and impose strong curvature at edges of flat cisternae and along tubules (Voeltz et al., 2006). How forces that shape ER are balanced to achieve required form is under active investigation, but Ire1 is again implicated by observations in yeast Journal of Cell Science @BULLET Advance article that although Ire1 mutants have normal ER morphology in the absence of ER stress, when stressed they produce tangled knots of irregular, reticulon-rich ER tubules (Schuck et al., 2009). Developing Drosophila photoreceptors (R cells) are a favorable venue for studies of ER dynamics. "
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    • "Previous reports have shown that ER volume may increase up to fivefold during UPR and is driven by lipid biosynthesis. The increased ER volume is in itself an important part of the UPR response, making protein aggregation (due to misfolding) less likely and to accommodate the increased synthesis of ER chaperones (Schuck et al., 2009). However, at the light microscopic level, the intracellular redistribution of the ATP-sensitive Kþ channels visualized by fluorescent Glibenclamide staining of thapsigargin treated cells was not reproduced in infected cells. "
    Dataset: ER stress

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    • "Previous reports have shown that ER volume may increase up to fivefold during UPR and is driven by lipid biosynthesis. The increased ER volume is in itself an important part of the UPR response, making protein aggregation (due to misfolding) less likely and to accommodate the increased synthesis of ER chaperones (Schuck et al., 2009). However, at the light microscopic level, the intracellular redistribution of the ATP-sensitive Kþ channels visualized by fluorescent Glibenclamide staining of thapsigargin treated cells was not reproduced in infected cells. "
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