14 Mar 2014
Thomas Shemesh
Rapoport Lab, Department of Cell Biology
Harvard Medical School
The peripheral endoplasmic reticulum (ER) is an extensive membrane structure that is found in eukaryote cells, and is the site for many key biological functions: folding and maturation of secretion-bound proteins, lipid synthesis and Ca2+ regulation. The ER forms a continuous membrane system with a common internal space, and consists of domains that can adopt different morphologies, such as: tubules, flat sheets, sheets with holes (fenestrations), and stacked sheets. We show that the generation of tubules and sheets can be explained by curvature-stabilizing proteins, such as the reticulons, which stabilize the high membrane curvature of tubule crosss-sections and sheet edges. We develop an elasticity-based model for the composite membrane-protein system, and relate the observed morphologies to its equilibrium states. We employ our model to explain the formation of virtually all observed ER morphologies on the basis of two types of curvature-stabilizing proteins, which differ in the preferred curvature of the edge line. Our model shows that, in a mostly tubular network with an abundance of both types of proteins, three-way junctions are energetically favored, in agreement with experimental observations in interphase Xenopus egg extracts. At low concentrations of edge producing proteins, sheets connected to multiple tubules are favored, consistent with the experimentally observed shape of the mitotic ER. In addition, fenestrations or helicoidal connections can be generated. Our model suggests how ER morphologies are interconverted in response to the metabolic state or cell cycle phase of a cell.