KAI SIMONS DE
Max-Planck-Institute of Molecular Cell Biology and Genetics, Dresden, Germany
Saturday, 21 September, 17:45-18:30, Auditorium
Cell Membranes : Subcompartmentalization driven by phase separation
Cell membranes have developed a tremendous complexity of lipids and proteins geared to perform the functions cells require. To coordinate these functions, the bilayer has evolved the propensity to segregate its constituents laterally. This capability is based on dynamic liquid-liquid immiscibility and underlies the raft concept of membrane sub-compartmentalization. The potential for sphingolipid-cholesterol self-assembly combines with protein specificity to dynamically regulate protein segregation within the membrane plane. This mechanism is employed in regulating endocytic or exocytic membrane transport, in transducing specific signals across the plasma membrane or to perform different biochemical reactions dependent on the proteins involved. The regulation of the two dimensional separation of lipids and proteins in membranes into dynamic liquid membrane rafts is dependent on the propensity for liquid phase separation. The most dramatic demonstration of phase separation in a cell membrane comes from our work on plasma membrane spheres produced by hypotonic swelling. We can induce giant domains enriched in the ganglioside GM1 by pentavalent cholera toxin-crosslinking at 37°C. This domain formation is cholesterol-dependent and the GM1 phase is enriched in raft proteins and excludes non-raft proteins. Thus, plasma membranes can phase separate into large micrometer domains like model membranes do. However, in contrast to phase–segregating plasma membranes, transmembrane raft proteins are excluded from the liquid-ordered raft-like phase in model membranes. The selective inclusion of transmembrane proteins in the raft phase suggests that this phase possesses other functional qualities in addition to the lipid basis for liquid-ordered/ disordered phase separation seen in model membranes. Most importantly, cellular plasma membranes seem to be poised close to a phase transition, facilitating dynamic sub-compartmentalization with little energetic cost. Liquid phase transitions are not confined to cell membranes as the plenary session following my opening lecture will highlight. Liquid phase transitions are emerging as a general principle driving cellular organisation.
Kai Simons received his MD degree from the University of Helsinki. Simons then conducted postdoctoral research at Rockefeller University in New York. In 1967, he was Principal Investigator of the Finnish Medical Research Council at the University of Helsinki. In 1975, he moved to the European Molecular Biology Laboratory (EMBL) in Heidelberg, German, where he started the Cell Biology Program, which became the focal point for molecular cell biology in Europe. In 2001 Kai Simons moved to Dresden to build up the new Max Planck Institute for Molecular Cell Biology and Genetics. This Institute is today an internationally recognized center in its area of research. His recent research has focused on cell membrane organization and function. He has pioneered the concept of lipid rafts as a membrane organizing principle, based on the phase-separating capabilities of sphingolipids and cholesterol in cell membranes.