I. The Role of Lipids in Organizing the Cellular Traffic
II. Lipid Rafts as a Membrane Organizing Principle
III. Biogenesis of Glycolipid-Rich Apical Membranes
Part I: The Role of Lipids in Organizing the Cellular Traffic
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Simons begins by explaining that cholesterol and sphingolipids are made in the ER and the Golgi complex, respectively and then transported to various membranes in the cell. This sorting leads to an increased concentration of cholesterol and sphingolipids in the plasma membrane relative to other membranes. In the Golgi cholesterol and sphingolipids tend to cluster together to form lipid rafts for transport to the plasma membrane. Since certain proteins associate with cholesterol and sphingolipids, this lipid sorting directs the movement of proteins within the cell. In the second part of his talk, Simons describes mechanisms by which small nanoscale rafts can coalesce to form larger stabilized rafts that function in different cellular processes e.g. signal transduction, membrane trafficking and cell polarization. He also describes how processes such as palmitoylation and GPI-anchoring regulate the association of proteins with rafts. In Part 3, Simons demonstrates how proteins and glycolipids segregate to the apical domain in epithelial cells to support cell polarization.
Kai Simons received his M.D. from the University of Helsinki and pursued postdoctoral research at Rockefeller University in New York. He then returned to the University of Helsinki before moving to the newly formed EMBL in 1975 where he was the coordinator of the Cell Biology Program. In 1998, Simons became a director of the Max-Planck-Institute of Molecular Cell Biology and Genetics in Dresden where he continues to work as a group leader today.
Early in his career, 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.
Simons’ contributions have been recognized with numerous awards including membership in the National Academy of Sciences, USA and the German Academy of Sciences, Leopoldina.
- Satyajit Mayor iBioSeminar: Membrane Rafts
- Jennifer Lippincott-Schwartz iBioMagazine: How Do Lipids and Cholesterol Regulate Trafficking Across the Secretory Pathway
- Kai Simons iBioMagazine: High Tech and Low Tech
- Randy Schekman iBioSeminar: The Secretory Pathway
- Youreka Science: The cell's radar: how cells sense their environment
Simons K, Gerl, MJ (2010). Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol. 11(10):688-99.
Lingwood, D, Simons, K (2010). Lipid rafts as a membrane-organizing principle. Science. 327(5961):46-50.
Coskun U, Grzybek M, Drechsel D, Simons K. (2011). Regulation of human EGF receptor by lipids. Proc Natl Acad Sci 108(22):9044-8.
Mishra R, Grzybek M, Niki T, Hirashima M, Simons K (2010), Galectin-9 trafficking regulates apico-basal polarity in MDCK epithelial cells. Proc Natl Acad Sci. 107(41):17633:17638.