Schuck Sebastian, Prinz William A, Thorn Kurt S, Voss Christiane, Walter Peter
Howard Hughes Medical Institute and Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
J Cell Biol. 2009 Nov 16;187(4):525-36. doi: 10.1083/jcb.200907074. Epub 2009 Nov 9.
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.
细胞会根据需要不断调整其细胞器的大小和形状。在本研究中，我们检测了酿酒酵母在未折叠蛋白反应（UPR）过程中内质网（ER）膜的扩张情况。我们发现膜扩张通过内质网片层的产生而发生，需要UPR信号传导，并由脂质生物合成驱动。将内质网大小控制与UPR解偶联表明，膜扩张可独立于内质网伴侣水平的增加来减轻内质网应激。通过过表达网织蛋白将扩张的内质网片层转化为小管并不影响细胞应对内质网应激的能力，这表明内质网的大小而非形状是关键因素。因此，通过膜合成增加内质网大小是细胞克服内质网应激程序中不可或缺且独特的一部分。
