Lipid rafts are membrane microdomains that are enriched in cholesterol and glycosphingolipids. They have been implicated in processes as diverse as signal transduction, endocytosis and cholesterol trafficking. Recent evidence suggests that this diversity of function is accompanied by a diversity in the composition of lipid rafts. The rafts in cells appear to be heterogeneous both in terms of their protein and their lipid content, and can be localized to different regions of the cell. This review summarizes the data supporting the concept of heterogeneity among lipid rafts and outlines the evidence for cross-talk between raft components. Based on differences in the ways in which proteins interact with rafts, the Induced-Fit Model of Raft Heterogeneity is proposed to explain the establishment and maintenance of heterogeneity within raft populations.

Abbreviations used: CAP, Cbl-associated protein; DIG, detergent-insoluble, glycosphingolipid-enriched membrane; DRM, detergent-resistant membrane; GFP, green fluorescent protein; GPI, glycosylphosphatidylinositol; HA, haemagglutinin; MDCK, Madin–Darby canine kidney; SoHo, sorbin homology.

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