title: A model for the generation and interconversion of ER morphologies.
abstract: The peripheral endoplasmic reticulum (ER) forms different morphologies composed of tubules and sheets. Proteins such as the reticulons shape the ER by stabilizing the high membrane curvature in cross-sections of tubules and sheet edges. Here, we show that membrane curvature along the edge lines is also critical for ER shaping. We describe a theoretical model that explains virtually all observed ER morphologies. The model is based on two types of curvature-stabilizing proteins that generate either straight or negatively curved edge lines (R- and S-type proteins). Dependent on the concentrations of R- and S-type proteins, membrane morphologies can be generated that consist of tubules, sheets, sheet fenestrations, and sheet stacks with helicoidal connections. We propose that reticulons 4a/b are representatives of R-type proteins that favor tubules and outer edges of sheets. Lunapark is an example of S-type proteins that promote junctions between tubules and sheets. In a tubular ER network, lunapark stabilizes three-way junctions, i.e., small triangular sheets with concave edges. The model agrees with experimental observations and explains how curvature-stabilizing proteins determine ER morphology.
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tomsh@technion.ac.il.
authors.forename: Tom
authors.initials: T
authors.lastname: Shemesh
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Robin W
authors.initials: RW
authors.lastname: Klemm
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Fabian B
authors.initials: FB
authors.lastname: Romano
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Songyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138; and.
authors.forename: Joshua
authors.initials: J
authors.lastname: Vaughan
authors.affiliation: Howard Hughes Medical Institute and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138; and.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
authors.forename: Hanna
authors.initials: H
authors.lastname: Tukachinsky
authors.affiliation: Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kozlov
authors.affiliation: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tom_rapoport@hms.harvard.edu.
authors.forename: Tom A
authors.initials: TA
authors.lastname: Rapoport
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004548:Elasticity; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000737:chemistry; D006801:Humans; D021621:Imaging, Three-Dimensional; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D011487:Protein Conformation; D034622:RNA Interference; D013997:Time Factors; D014982:Xenopus laevis
chemical_list: D018398:Homeodomain Proteins; C474231:LNPK protein, human; D008565:Membrane Proteins
keywords: endoplasmic reticulum; lunapark; model; morphology; reticulon