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KEY WORDS: membrane domain, glycosphingolipid, GPI-anchored protein, signal transduction, membrane trafficking
ABSTRACT
Recent studies showing that detergent-resistant membrane fragments can be isolated from cells suggest that biological membranes are not always in a liquidcrystalline 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.
INTRODUCTION
Because most biological phospholipids have low acyl chain melting temperatures (Tm), cellular membranes are generally thought to exist in a fluid, liquidcrystalline (lc) phase. However, the plasma membrane and some organelles of the secretory and endocytic pathways in eukaryotic cells are rich in sphingolipids, which have elevated Tm, and sterols, which can have profound effects on membrane phase (Silvius et al 1996). This mixture of lipids raises the possibility of complex phase behavior in these membranes.
In fact, a number of recent studies suggest that eukaryotic cell plasma membranes are not entirely in the conventional 1c phase (Brown & London 1998). Instead, they may be, at least partially, in the cholesterol-rich liquid-ordered (lo) phase. The lo phase is characterized by a high degree of acyl chain order and is favored by high-Tm lipids with saturated acyl chains such as sphingolipids, when they are mixed with cholesterol. The strongest experimental support for this idea has come from a seemingly unrelated finding; i.e. in the cold, plasma membranes are partially resistant to solubilization by non-ionic detergents such as Triton X-100 (Brown & London 1998). After Triton extraction, insoluble lipids remain in the form of detergent-resistant membranes (DRMs; also called detergent-insoluble glycolipid-enriched membranes or DIGs) (Simons & Ikonen 1997).
We recently reviewed the evidence equating DRMs and lipid bilayers...