The role of lipid rafts in trimeric G protein-mediated signal transduction

Lipid rafts and caveolae are microdomains in the cell membranes, which contain cholesterol, glycolipids, and sphingomyelin. While caveolae are relatively stable because caveolin, an integral protein, supports the structure, lipid rafts are considered to be unstable, being dynamically produced and degraded. Recent studies have reported that lipid rafts contain many signaling molecules, such as glycosylphosphatidylinositol-anchored proteins, acylated proteins, G-protein-coupled receptors (GPCRs), trimeric and small G-proteins and their effectors, suggesting that the lipid rafts have an important role in receptor-mediated signal transduction. Therefore drugs that modify the composition of lipid rafts might influence the efficacy of cellular signal transduction. In this review, we demonstrate the role of lipid rafts in GPCR-G-protein signaling and also present our recent results showing that the wasp toxin mastoparan modifies G(q/11)-mediated phospholipase C activation through the interaction with gangliosides in lipid rafts.