Lipid Raft - History

History

Until 1982, it was widely accepted that phospholipids and membrane proteins were randomly distributed in cell membranes, according to the Singer-Nicolson fluid mosaic model, published in 1972. However, membrane microdomains were postulated in the 1970s using biophysical approaches by Stier & Sackmann and Klausner & Karnovsky. These microdomains were attributed to the physical properties and organization of lipid mixtures by Stier & Sackmann and Israelachvili et al. In 1974, the effects of temperature on membrane behavior had led to the proposal of "clusters of lipids" in membranes and by 1975, data suggested that these clusters could be "quasicrystalline" regions within the more freely dispersed liquid crystalline lipid molecule. In 1978, X-Ray diffraction studies led to further development of the "cluster" idea defining the microdomains as "lipids in a more ordered state". Karnovsky and co-workers formalized the concept of lipid domains in membranes in 1982. Karnovsky's studies showed heterogeneity in the lifetime decay of 1,6-diphenyl-1,3,5-hexatriene, which indicated that there were multiple phases in the lipid environment of the membrane. One type of microdomain is constituted by cholesterol and sphingolipids. They form because of the segregation of these lipids into a separate phase, demonstrated by Biltonen and Thompson and their coworkers. These microdomains (‘rafts’) were shown to exist also in cell membranes. Later, Kai Simons at the European Molecular Biology Laboratory (EMBL) in Germany and Gerrit van Meer from the University of Utrecht, Netherlands refocused interest on these membrane microdomains, enriched with lipids and cholesterol, glycolipids, and sphingolipids, present in cell membranes. Subsequently, they called these microdomains, lipid "rafts". The original concept of rafts was used as an explanation for the transport of cholesterol from the trans Golgi network to the plasma membrane. The idea was more formally developed in 1997 by Simons and Ikonen. At the 2006 Keystone Symposium of Lipid Rafts and Cell Function, lipid rafts were defined as "small (10-200nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein interactions" In recent years, lipid raft studies have tried to address many of the key issues that cause controversy in this field, including the size and lifetime of rafts.

Other questions yet to be answered include:

• What are the effects of membrane protein levels?
• What is the physiological function of lipid rafts?
• What effect does flux of membrane lipids have on raft formation?
• What effect do diet and drugs have on lipid rafts?
• What effect do proteins located at raft boundaries have on lipid rafts?