The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Kai Simons, M.D., research group leader and director emeritus, Max Planck Institute of Molecular Cell Biology and Genetics

Speaker bio(s)

The lipid raft concept introduces into membrane organization the capability of dynamic subcompartmentalization based on phase separation. Rafts form dynamic platforms with a key role in regulating membrane functions. They are dynamic assemblies of sphingolipids, cholesterol and proteins that dissociate and associate. These assemblies can be induced to coalesce to form raft clusters and these are the platforms that function in membrane trafficking, cell polarization and signaling. The most dramatic demonstration of phase separation in a cell membrane comes from the work of Dr. Simons' lab on plasma membrane spheres produced by hypotonic swelling. He and his colleagues can induce large domains enriched in the gangliosides GM1 by pentavalent cholera toxin-crosslinking at 37C. This domain formation is cholesterol-dependent and the GM1 phase is enriched in raft proteins and excludes non-raft proteins. Plasma membranes thus can phase separate like model membranes, but they differ in one key property. In contrast to the phase-segregating plasma membrane spheres, the transmembrane raft proteins are excluded from the Lo phase in model membranes. The selective inclusion of transmembrane proteins in the raft phase suggests that this phase possesses a quality in addition to the lipid basis for Lo-Ld phase separation seen in model membranes. To study the protein-lipid interactions that govern partitioning of transmembrane proteins in and out of raft microdomains in membranes Dr. Simons and his colleagues have expressed and purified the EGF receptor. They now have evidence that the ganglioside GM3 in the raft phase in reconstituted proteoliposomes inhibits the tyrosine kinase activity of the receptor after EGF addition. Their working model is that transmembrane proteins become raftophilic by being lubricated by binding to raft lipids and that this capability is regulated by palmitoylation. Dr. Simons will describe his lab's work demonstrating how rafts function in membrane trafficking to the cell surface, particularly how they contribute to apical membrane biogenesis as originally postulated.

Dr. Simons received his M.D. from the University of Helsinki and pursued postdoctoral research in Alexander Bearn's lab at Rockefeller University. He returned to the University of Helsinki before moving to the newly formed European Molecular Biology Laboratory in 1975, where he was the coordinator of the Cell Biology Program. In 1998, Dr. Simons joined the Max Planck Institute of Molecular Cell Biology and Genetics as its founding director and group leader.

Early in his career, Dr. Simons used Semliki Forest Virus to study the detergent solubilization of lipid membranes as well as assembly of the virus in the host cell. Later, he began to investigate the sorting of lipids and proteins in polarized cells. He is the father of the concept of lipid rafts as a mechanism to organize cell membranes.

Dr. Simons' contributions have been recognized with numerous awards including membership in the U.S. National Academy of Sciences and the German Academy of Sciences.

Open to

Public

Host

Gunter Blobel

Contact

Robert Houghtaling

Phone

(212) 327-8072

Sponsor

Robert Houghtaling
(212) 327-8072
rhoughtali@rockefeller.edu