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Lipid raft heterogeneity: an enigma

Glycosphingolipids (GSLs) and glycoproteins are ubiquitous components of mammalian cell membranes. GSLs are especially enriched in the nervous system and significantly contribute to membrane organization and a variety of cellular functions. Current body of evidence suggests that GSLs along with cholesterol are enriched in discrete membrane domains that associate specific proteins. Current notion of membrane organization is that, the GSL–cholesterol‐enriched membrane domains known as ‘lipid rafts’ float in the phospholipid‐enriched bulk of the membrane and regulate the cell signaling by facilitating the lipid–protein/protein–protein interactions. The sizeable literature accumulated during the last decade has provided some insight into the organization and function of rafts; however, they still remain perplexing. In recent years, an appealing concept of lipid raft heterogeneity has emerged. GSL‐ and glycosylphosphatidylinositol‐anchored proteins are considered as the crucial pivots of heterogeneous rafts. This review deals with the enigma of organizational and functional heterogeneity of lipid rafts and discusses the dynamic coalescence of heterogeneous rafts during signaling that can explain the specificity of raft‐regulated cellular signaling events.