Biologia celular

Lipid Rafts As a Membrane-Organizing Principle Daniel Lingwood, et al. Science 327, 46 (2010); DOI: 10.1126/science.1174621

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REVIEW Lipid Rafts As a MembraneOrganizing Principle
Daniel Lingwood and Kai Simons* Cell membranes display a tremendous complexity of lipids and proteins designed to perform the functions cells require. To coordinate these functions, the membrane is able to laterally segregate its constituents. This capability is basedon dynamic liquid-liquid immiscibility and underlies the raft concept of membrane subcompartmentalization. Lipid rafts are fluctuating nanoscale assemblies of sphingolipid, cholesterol, and proteins that can be stabilized to coalesce, forming platforms that function in membrane signaling and trafficking. Here we review the evidence for how this principle combines the potential forsphingolipid-cholesterol self-assembly with protein specificity to selectively focus membrane bioactivity. he lipid raft hypothesis proposes that the lipid bilayer is not a structurally passive solvent, but that the preferential association between sphingolipids, sterols, and specific proteins bestows cell membranes with lateral segregation potential. The concept has long suffered assessment by indirect means,leading to questions of fact or artifact (1). The resistance of sphingolipid, cholesterol, and a subclass of membrane proteins to cold detergent extraction (2) or mechanical disruption (3) has been widely used as an index for raft association with little or no regard for the artifacts induced by these methods. Though the acquisition of resistance to disruption may point to physiologically relevantbiases in lateral composition (4), this disruptive measure tells us little about native membrane organization. Support from light microscopy was also missing because, with the exception of organization into specialized membrane domains such as caveolae or microvilli, putative raft components—specifically glycosylphosphatidylinositol (GPI)–anchored proteins, fluorescent lipid analogs, rafttransmembrane (TM) domains, and acylated proteins—often show a homogeneous distribution at the cell surface (5). Moreover, early investigations into submicron membrane organization often yielded conflicting evidence regarding the distribution or motion of these constituents in the living cell (1). Today, however, the advancement of technology has produced compelling data that self-organization of lipids...