Flying kites on slippery slopes at Keystone

Introduction The fluid-mosaic model of the plasma membrane, proposed by Singer and Nicolson in the early 1970s (Singer & Nicolson, 1972), has provided a powerful driving force for understanding the structure of the cell membrane. Studies of the temporal and spatial architecture of the plasma membrane have indicated that it consists of compartments, which are probably maintained through their interaction with the underlying cortical cytoskeleton meshwork (Edidin, 2003; Kusumi et al, 2005). The membrane raft hypothesis was originally proposed by Simons and van Meer to explain the segregation of lipids and membrane proteins during their delivery and distribution in polarized epithelium (Simons & van Meer, 1988). This hypothesis—according to which specific lipids dynamically associate with each other to form platforms that are important for membrane-protein sorting and the formation of signalling complexes—was then integrated with the observed compartments (Simons & Toomre, 2000). Subsequently, this type of compartmentalization was related to studies of artificial membranes showing phase segregation behaviour, in which lipids in a fluid bilayer separate into domains containing molecules that display more or less ordered organization in terms of correlation with the orientation of neighbouring molecules (Simons & Vaz, 2004). This conference focused on lipid rafts and caveolar domains that occur in biomembranes. There are many models for lipid rafts, ranging from lipid shells and nanoscopic domains to the predominantly ordered plasma membrane (Anderson & Jacobson, 2002; Edidin, 2003; Hancock, 2006). However, many questions about lipid rafts remain, including the structure of these domains, their size and distribution in the membrane, their mechanism of formation and their functional significance, if any. In this report, we discuss new developments in the understanding of the lateral segregation of lipids that have been obtained from studies using artificial membranes and the parallel efforts to visualize lipid-dependent protein assemblies in living-cell membranes. We also report on new information regarding the various roles of lipid rafts in many cellular processes, such as membrane trafficking and signal transduction, the anchorage of rafts to the actin cytoskeleton, and the involvement of caveloae and caveolin-1 in cell function.