Mechanisms Determining the Morphology of the Peripheral ER

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2010.11.007 Byline: Yoko Shibata (1)(2), Tom Shemesh (3), William A. Prinz (4), Alexander F. Palazzo (1)(5), Michael M. Kozlov (3), Tom A. Rapoport (1)(2) Abstract: The endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by the curvature-stabilizing proteins reticulons and DP1/Yop1p, but how the sheets are formed is unclear. Here, we identify several sheet-enriched membrane proteins in the mammalian ER, including proteins that translocate and modify newly synthesized polypeptides, as well as coiled-coil membrane proteins that are highly upregulated in cells with proliferated ER sheets, all of which are localized by membrane-bound polysomes. These results indicate that sheets and tubules correspond to rough and smooth ER, respectively. One of the coiled-coil proteins, Climp63, serves as a 'luminal ER spacer' and forms sheets when overexpressed. More universally, however, sheet formation appears to involve the reticulons and DP1/Yop1p, which localize to sheet edges and whose abundance determines the ratio of sheets to tubules. These proteins may generate sheets by stabilizing the high curvature of edges. Author Affiliation: (1) Howard Hughes Medical Institute, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA (2) Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA (3) Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, 69978 Tel Aviv, Israel (4) Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Disorders, National Institute of Health, Bethesda, MD 02892, USA (5) Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada Article History: Received 19 May 2010; Revised 3 September 2010; Accepted 26 October 2010 Article Note: (miscellaneous) Published: November 24, 2010