Emerging Themes in Lipid Rafts and Caveolae

Lipid rafts are localized mainly at the level of the plasma-membrane, but they can also form within internal membrane compartments, such as the Golgi appara-Lipid Rafts, Caveolae, and Caveolins For many years, scientists viewed the lipid bilayer of the tus (Gkantiragas et al., 2001). Therefore, the partitioning of caveolins into these liquid-ordered domains may be-plasma membrane as a two-dimensional " fluid mosaic " (Singer and Nicolson, 1972). In this so-called " liquid-gin to occur at the level of the Golgi apparatus, initiating the biogenesis of caveolae. The current working hypoth-crystalline state, " packing is loose and lateral diffusion is relatively rapid (Gennis, 1989; Lee, 1977). The impli-esis is that lipid rafts may represent precursors of caveo-lae that facilitate the cholesterol-dependent insertion of cation of such a model is that all plasma membrane proteins are considered to be uniformly dispersed in the caveolins into membranes. Caveolae are found in many cell types but are particularly abundant in fibroblasts, lipid solvent, akin to " icebergs in a sea of lipid. " Many independent investigators in the past decade, however, adipocytes, endothelial cells, type I pneumocytes, epi-thelial cells, and smooth and striated muscle cells (Smart have provided evidence for the existence of other lipid bilayer states, namely " liquid-ordered " membranes. et al., 1999). The mammalian caveolin gene family consists of caveolin-1,-2, and-3. Caveolins-1 and-2 are These regions are enriched in cholesterol and sphingoli-pids (Table 1), making them more ordered and less fluid coexpressed and form a heterooligomeric complex in many cell types, with particularly high levels in adipo-than the bulk plasma membrane. As a consequence, these membranes are resistant to solubilization with nonionic cytes, whereas expression of caveolin-3 is muscle-specific and found in both cardiac and skeletal muscle, as detergents at low temperatures (Brown and London, 1997; Moldovan et al., 1995). These liquid-ordered mi-well as smooth muscle cells (Smart et al., 1999). These caveolin homo-and heterooligomers directly interact crodomains of the plasma-membrane have been termed lipid rafts (Figure 1A). However, lipid rafts have also been with cholesterol and represent the functional assembly units of caveolae (Figure 1B). In addition, the caveolin referred to in the literature by many different names: detergent-insoluble glycolipid-rich domains (DIGs), gly-gene family is structurally and functionally conserved from worms (C. elegans) to humans, supporting the idea colipid-enriched membranes (GEMs), and low-density Triton-insoluble (LDTI) complexes. It is now clear that that caveolins play an important role in modulating raft …