A model for the generation and interconversion of ER morphologies

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.