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Sculpting Cell Membranes: Understanding pathways of endocytosis and exocytosis

Seminar by Prof. Harvey McMahon, Medical Research Council, Cambridge.

Abstract
Cell shape is adapted to function. Organelle shape is likewise optimised for the processes that take place on and within these microenvironments. We focus on the dynamic regulation of membrane shape, which can occur by the interplay between the transient and regulated insertion of membrane bending proteins (e.g. ENTH domains/amphipathic helices) and the detection and stabilisation of membrane curvature by BAR-containing proteins and other like-molecules. We have solved the structures of a number of these protein modules, and have defined the molecular pathways on which they function. We can now go from the biophysics of a molecule to the molecular characterisation of novel cellular trafficking pathways both of endocytosis and exocytosis.

Ford, M.G., Mills, I.G., Peter, B.J., Vallis, Y., Praefcke, G.J., Evans, P.R. and McMahon, H.T. (2002) Curvature of clathrin-coated pits driven by epsin. Nature, 419, 361-366.

Peter, B.J., Kent, H.M., Mills, I.G., Vallis, Y., Butler, P.J., Evans, P.R. and McMahon, H.T. (2004) BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science, 303, 495-499.

Jochusch, W.J., Praefcke, G.J.K., (McMahon, H.T. and Lagnado, L.) (2005) Clathrin-dependent and clathrinindependent retrieval of synaptic vesicles in retinal bipolar cells. Neuron 46, 869-878

Gallop, J.L., Jao, C.C., Kent, H.M., Butler, P.J.G., Evans, P.R., Langen, R. and McMahon, H.T. (2006) Mechanism of endophilin N-BAR domain-mediated membrane curvature. EMBO J. 25, 2898-2910.

Sascha Martens, Michael M. Kozlov and Harvey T. McMahon (2007) How Synaptotagmin Promotes Membrane Fusion. Science. Published online 3 May 2007; 10.1126/science.1142614