Generation of Cubic Membranes by Controlled Homotypic Interaction of Membrane Proteins in the Endoplasmic Reticulum

Daniel Lingwood,Sebastian Schuck,Charles Ferguson,Mathias J Gerl,Kai Simons

doi:10.1074/jbc.m900220200

Abstract

Cell membranes predominantly consist of lamellar lipid bilayers. When studied in vitro, however, many membrane lipids can exhibit non-lamellar morphologies, often with cubic symmetries. An open issue is how lipid polymorphisms influence organelle and cell shape. Here, we used controlled dimerization of artificial membrane proteins in mammalian tissue culture cells to induce an expansion of the endoplasmic reticulum (ER) with cubic symmetry. Although this observation emphasizes ER architectural plasticity, we found that the changed ER membrane became sequestered into large autophagic vacuoles, positive for the autophagy protein LC3. Autophagy may be targeting irregular membrane shapes and/or aggregated protein. We suggest that membrane morphology can be controlled in cells.

Highlights

Since the application of electron microscopy (EM)3 to the study of cell ultrastructure, unusual membrane morphologies have been reported for virtually every organelle [14, 15]
Both endogenous LC3 and GFP-LC3 showed an even cytoplasmic distribution when IDER was expressed in the absence of the dimerizer. These observations suggest that Fv dimerization between membrane proteins in the endoplasmic reticulum (ER) may be related to an autophagic response wherein the ensuing organized smooth ER (OSER) whorls and sinusoids are removed from the ER
Direct template correlative matching later established that the sinusoidal ER architecture corresponded to a double diamond cubic symmetry [16]

Summary

Introduction

Since the application of electron microscopy (EM)3 to the study of cell ultrastructure, unusual membrane morphologies have been reported for virtually every organelle [14, 15]. Weak homotypic interactions between membrane proteins produce both a whorled and a sinusoidal OSER phenotype [38], the latter exhibiting a cubic symmetry [16, 39]. We were able to produce OSER with cubic membrane morphology via induction of homo-dimerization of artificial membrane proteins.

Results

Conclusion