Exocytosis and Endocytosis; from membranes and molecules to mechanisms
28 Nov 2013, 15:30. Sala 300
Exocytosis and Endocytosis; from membranes and molecules to mechanisms
Harvey T. McMahon
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
Cell shape is adapted to function. Organelle shape and local membrane architectures are 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 motifs and the detection and stabilisation of membrane shape. This approach has allowed us not only to describe the biophysics of membrane shape changes but also to take a fresh look at membrane dynamics in physiological processes like exocytosis and endocytosis. In doing so we have noted that proteins with amphipathic helices or hydrophobic membrane-inserting loops are likely to effect or respond to curvature and that the membrane interaction surfaces of proteins can sense shape (like proteins of the BAR Superfamily). This molecular view has allowed us to ascribe novel cell-biological functions to proteins (e.g. the mechanistic affect of synaptotagmin in membrane fusion) and to give a more insightful view of how these processes work. Thus we can now go from the biophysics of a molecule, to better understanding of known pathways and to the molecular characterisation of novel cellular trafficking pathways both of endocytosis and exocytosis. See: http://www.endocytosis.org/
References
Emmanuel Boucrot, Adi Pick, Gamze Çamdere, … Harvey T. McMahon, Michael M. Kozlov (2012) Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains. Cell 149(1),124-36. PMID: 22464325
William Mike Henne, Emmanuel Boucrot, … Harvey T. McMahon (2010) FCHo Proteins are Nucleators of Clathrin-Mediated Endocytosis. Science 328, 1281-1284. PMID: 20448150
Alexander J. Groffen, Sascha Martens, … (Harvey T. McMahon and Matthijs Verhage) (2010) Doc2b Is a High-Affinity Ca2+ Sensor for Spontaneous Neurotransmitter Release. Science 327(5973), 1614-1618. PMID: 20150444
Harvey T. McMahon, Misha Kozlov and Sascha Martens (2010) Membrane Curvature in Synaptic Vesicle Fusion and Beyond. Cell 140, 601-605. PMID: 20211126
Richard Lundmark, Gary J. Doherty, … Harvey T. McMahon (2008) The GTPase-activating protein GRAF1 regulates the CLIC/GEEC endocytic pathway. Current Biology 18, 1802-1808. PMID: 19036340
Sascha Martens, Michael M. Kozlov and Harvey T. McMahon (2007) How Synaptotagmin Promotes Membrane Fusion. Science 316, 1205-1208. PMID: 17478680
Eva M. Schmid and Harvey T. McMahon (2007) Integrating molecular and network biology to decode endocytosis. Nature 448, 883-888. PMID: 17713526
William Mike Henne, Helen M. Kent, … Philip R. Evans, and Harvey T. McMahon (2007) Structure and Analysis of FCHo2 F-BAR Domain: a Dimerising and Membrane Recruitment Module that Effects Membrane Curvature. Structure 15, 839-852. PMID: 17540576
Oli Daumke, Richard Lundmark, Yvonne Vallis, Sascha Martens, Jo Butler and Harvey T. McMahon (2007) Architectural and mechanistic insights into an EHD ATPase involved in membrane remodelling. Nature 449, 923-927. PMID: 17914359
