Membrane Shape Modulates Transmembrane Protein Distribution

• In vitro measurement of the effect of membrane shape on protein distribution
• Membrane curvature can induce significant sorting of typical TM proteins
• Effective protein shape/flexibility can be quantified by curvature-driven sorting
• Model predicts pervasive modulation of protein distribution/activity by curvature

SummaryAlthough membrane shape varies greatly throughout the cell, the contribution of membrane curvature to transmembrane protein targeting is unknown because of the numerous sorting mechanisms that take place concurrently in cells. To isolate the effect of membrane shape, we used cell-sized giant unilamellar vesicles (GUVs) containing either the potassium channel KvAP or the water channel AQP0 to form membrane nanotubes with controlled radii. Whereas the AQP0 concentrations in flat and curved membranes were indistinguishable, KvAP was enriched in the tubes, with greater enrichment in more highly curved membranes. Fluorescence recovery after photobleaching measurements showed that both proteins could freely diffuse through the neck between the tube and GUV, and the effect of each protein on membrane shape and stiffness was characterized using a thermodynamic sorting model. This study establishes the importance of membrane shape for targeting transmembrane proteins and provides a method for determining the effective shape and flexibility of membrane proteins.

Graphical AbstractFigure optionsDownload high-quality image (127 K)Download as PowerPoint slide