Membrane Curvature Regulates The Localization Of G Protein Coupled Receptors And Ras Isoforms

The shape of biological membranes (membrane curvature) has been recognized to regulate the binding and thus the spatial localization of soluble proteins containing BAR domains, amphipathic helices or lipid anchors1-3. However, with few exceptions4,5, the overwhelming majority of the experiments that have validated quantitatively sensing of membrane curvature have been performed with model reconstituted systems in vitro6-10, and thus strictly speaking remain inconclusive regarding the biological relevance of these measurements. Here I will discuss unpublished data on two new assays that allow quantitative characterization of membrane curvature in live cells. We exploited these assays to investigate the influence of membrane shape on the localization of transmembrane G protein coupled receptors and the three major isoforms of Ras (K-, N-, H-). Selected References (1) Madsen, K. L.; Bhatia, V. K.; Gether, U.; Stamou, D. FEBS Letters 2010, 584, 1848. (2) Baumgart, T.; Capraro, B. R.; Zhu, C.; Das, S. L. Annu. Rev. Phys. Chem. 2011, 62, 483. (3) Antonny, B. Annu. Rev. Biochem. 2011, 80, 101. (4) Ramamurthi, K. S.; Lecuyer, S.; Stone, H. A.; Losick, R. Science 2009, 323, 1354. (5) Galic, M. et al. Nat. Cell Biol. 2012, 14, 874. (6) Peter, B.; Kent, H.; Mills, I.; Vallis, Y.; Butler, P.; Evans, P.; McMahon, H. Science 2004, 303, 495. (7) Bigay, J.; Gounon, P.; Robineau, S.; Antonny, B. Nature 2003, 426, 563. (8) Tian, A.; Baumgart, T. Biophysical Journal 2009, 96, 2676. (9) Sorre, B.; Callan-Jones, A.; Manzi, J.; Goud, B.; Prost, J.; Bassereau, P.; Roux, A. Proceedings of the National Academy of Sciences 2012, 109, 173. (10) Hatzakis, N. S.; Bhatia, V. K.; Larsen, J.; Madsen, K. L.; Bolinger, P.-Y.; Kunding, A. H.; Castillo, J.; Gether, U.; Hedegård, P.; Stamou, D. Nat. Chem. Biol. 2009, 5, 835.