Abstract
Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins. These microdomains, called lipid rafts, are well known for their role in receptor signaling on the plasma membrane (PM) and are essential to such cellular functions as signal transduction and spatial organization of the PM. A number of disease states, including atherosclerosis and other cardiovascular disorders, may be caused by dysfunctional maintenance of lipid rafts. Lipid rafts do not occur only in the PM but also have been found in intracellular membranes and extracellular vesicles (EVs). Here, we focus on discussing newly discovered functions of lipid rafts and microdomains in intracellular membranes, including lipid and protein trafficking from the ER, Golgi bodies, and endosomes to the PM, and we examine lipid raft involvement in the production and composition of EVs. Because lipid rafts are small and transient, visualization remains challenging. Future work with advanced techniques will continue to expand our knowledge about the roles of lipid rafts in cellular functioning.
Highlights
Cellular membranes are not homogenous mixtures of proteins; rather, they are segregated into microdomains on the basis of preferential association between specific lipids and proteins
Cellular membranes are not homogenous mixtures of lipids and proteins, rather, they are composed of lipids and proteins, some of which segregate into lipid microdomains called lipid rafts, which are enriched in free cholesterol (FC) and glycosphingolipids, like SM, and are resistant to detergent extraction
Increased levels of FC and SM strongly suggest that the lipid profile of exosomes is more like lipid rafts, but it is unclear at this time if this lipid composition has functional significance or is related to the site of vesicle generation where the predominant composition is that of a lipid raft
Summary
Cellular membranes are not homogenous mixtures of lipids and proteins, rather, they are composed of lipids and proteins, some of which segregate into lipid microdomains called lipid rafts, which are enriched in free cholesterol (FC) and glycosphingolipids, like SM, and are resistant to detergent extraction. Society for Biochemistry and Molecular Biology, Inc. This article is available online at https://www.jlr.org review of lipid rafts in inflammatory receptor signaling and atherosclerosis [1], a great deal of information has emerged providing new insights into how lipid rafts affect a number of disease states. Because lipid rafts are mobile and “float” like an iceberg in the liquid-disordered lipid phase, they can associate to form larger raft-domains, when proteins that associate with liquid-ordered domains facilitate oligomerization of protein complexes Studies of both rabbit erythrocytes and Chinese hamster ovary cells suggest that PMs accommodate lipid rafts having different lipid packing and sizes [5, 6]. With the refinement of the super-resolution techniques, we are poised to discover new information on factors leading to how these elusive and highly dynamic structures condense and dissolve
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