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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

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2005.10.015 Byline: Leonid V. Chernomordik (1), Michael M. Kozlov (2) Abstract: During membrane fusion, the outer leaflets of the two membranes merge first, whereas the distal membrane leaflets remain separate until the opening of a fusion pore. This intermediate stage, called hemifusion, is a critical event shared by exocytosis, protein trafficking, and viral entry. Author Affiliation: (1) Section on Membrane Biology, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892 (2) Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel

Recent advances in super-resolution microscopy revealed the previously unknown nanoscopic level of organization of endoplasmic reticulum (ER), one of the most vital intracellular organelles. Membrane nanostructures of 10- to 100-nm intrinsic length scales, which include ER tubular matrices, ER sheet nanoholes, internal membranes of ER exit sites (ERES), and ER transport intermediates, were discovered and imaged in considerable detail, but the physical factors determining their unique geometrical features remained unknown. Here, we proposed and computationally substantiated a common concept for mechanisms of all ER nanostructures based on the membrane intrinsic curvature as a primary factor shaping the membrane and ultra-low membrane tensions as modulators of the membrane configurations. We computationally revealed a common structural motif underlying most of the nanostructures. We predicted the existence of a discrete series of equilibrium configurations of ER tubular matrices and recovered the one corresponding to the observations and favored by ultralow tensions. We modeled the nanohole formation as resulting from a spontaneous collapse of elements of the ER tubular network adjacent to the ER sheet edge and calculated the nanohole dimensions. We proposed the ERES membrane to have a shape of a super flexible membrane bead chain, which acquires random walk configurations unless an ultra-low tension converts it into a straight conformation of a transport intermediate. The adequacy of the proposed concept is supported by a close qualitative and quantitative similarity between the predicted and observed configurations of all four ER nanostructures. [ABSTRACT FROM AUTHOR]