1. Academic Validation
  2. A model for the generation and interconversion of ER morphologies

A model for the generation and interconversion of ER morphologies

  • Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):E5243-51. doi: 10.1073/pnas.1419997111.
Tom Shemesh 1 Robin W Klemm 2 Fabian B Romano 2 Songyu Wang 2 Joshua Vaughan 3 Xiaowei Zhuang 3 Hanna Tukachinsky 2 Michael M Kozlov 4 Tom A Rapoport 5
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tomsh@technion.ac.il.
  • 2 Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
  • 3 Howard Hughes Medical Institute and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138; and.
  • 4 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
  • 5 Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tom_rapoport@hms.harvard.edu.
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.

Keywords

endoplasmic reticulum; lunapark; model; morphology; reticulon.

Figures