Functions of Lipid Rafts in Biological Membranes

Abstract

Recent studies showing that detergent-resistant membrane fragments can be isolated from cells suggest that biological membranes are not always in a liquid-crystalline phase. Instead, sphingolipid and cholesterol-rich membranes such as plasma membranes appear to exist, at least partially, in the liquid-ordered phase or a phase with similar properties. Sphingolipid and cholesterol-rich domains may exist as phase-separated "rafts" in the membrane. We discuss the relationship between detergent-resistant membranes, rafts, caveolae, and low-density plasma membrane fragments. We also discuss possible functions of lipid rafts in membranes. Signal transduction through the high-affinity receptor for IgE on basophils, and possibly through related receptors on other hematopoietic cells, appears to be enhanced by association with rafts. Raft association may also aid in signaling through proteins anchored by glycosylphosphatidylinositol, particularly in hematopoietic cells and neurons. Rafts may also function in sorting and trafficking through the secretory and endocytic pathways.

The Role of Sphingolipids and Ceramide in Pulmonary Inflammation in Cystic Fibrosis

“…Based on biophysical experiments determining the melting temperatures of lipids, Singer and Nicolson introduced the classical fluid mosaic model in 1972 predicting free movement of proteins in the lipid bilayer [31]. However, this concept was revised in the last 10-15 years and present concepts indicate the existence of distinct membrane domains [32, 33]. Sphingolipids interact with each other and with cholesterol molecules via hydrophilic interactions between the sphingolipid headgroups and the hydroxy group in the cholesterol molecule, respectively, and via hydrophobic van der Waal interactions between ceramide moieties and the sterol ring system [32-35].…”

Lipid rafts, cholesterol, and the brain

“…In particular, DRMs are thought to represent liquid-ordered (L o ) domains, which coexist in the same membrane with liquid disordered (L d ) domains (Schroeder et al 1994;Brown and London 1998). L o domains form due to the preferential interactions of sphingolipids and/or phospholipids containing saturated acyl chains with cholesterol (Brown and London 1998;Rietveld and Simons 1998).…”

“…L o domains form due to the preferential interactions of sphingolipids and/or phospholipids containing saturated acyl chains with cholesterol (Brown and London 1998;Rietveld and Simons 1998). In this state, lipids are tightly packed such that their order is close to that observed in the gel state, yet can undergo rapid lateral diffusion (Brown and London 1998). The characteristic features of liquid ordered domains, as well as the phase behavior of mixtures of liquid-ordered and liquid-disordered domains, can be easily studied in simple mixtures of purified lipids (London 2002;Silvius 2003;Veatch and Keller 2005).…”

“…Since the advent of the raft hypothesis, the list of putative raft-mediated events has grown at a rapid pace. Initially proposed to function primarily in protein sorting events in polarized cells, lipid rafts are now thought to regulate membrane trafficking in both the exocytic and endocytic pathways, cell migration, and a variety of cell signaling cascades (Brown and London 1998;Simons and Toomre 2000). Lipid-lipid interactions are thought to be of fundamental importance to the formation of lipid rafts, with cholesterol playing a special role as the "glue" that holds these domains together (Barenholz 2002).…”

Sphingolipids and membrane biology as determined from genetic models

“…However, the lack of genetic model systems that would permit molecular analyses impaired rapid progress in understanding the role of sphingolipids in the etiopathogenesis of these syndromes. In the mean-time, however, in vitro studies began to provide convincing evidence that sphingolipid metabolites function as second messengers [5][6][7][8][9] and that they influence signal-transduction events through their ability to segregate the plasma membrane into microdomains [10][11][12]. In addition, complex sphingolipids were shown to act as receptors to permit the entry of microorganisms into the cell and to alter the sensitivity of cells to cell-surface ligands [13][14][15].…”