ABSTRACT
The plasma membrane bilayer plays a central role in cellular signaling: it not only establishes the spatial segregation between the extracellular and cytosolic compartments but also harbors transmembrane receptors, adaptors, and effectors, and serves to anchor membrane-associated scaffolds that are involved in many signal transduction pathways.1-4 It is now clear that, far from being disordered, the plasma membrane is a complex, highly organized yet dynamic structure, whose components are continuously reorganized. Proteins and lipids are spatially segregated in dened micrometer-and nanometer-scale regions of the cell membrane.5,6
Data collected during the past years suggest that, in all likelihood, not only the plasmalemma but also endomembranes are segregated into dynamic nanodomains. Notably, previous studies have shown that endosomes act as intracellular signal transduction hubs with distinct subdomains.7,8 In addition, proteins that leave the endoplasmic reticulum emerge as export complexes at specialized exit sites, where they accumulate in transport carriers. These structures then transit from the reticulum intermediate compartment to the Golgi apparatus, where they fuse with the cis cisternae.9 While such endomembrane nanodomains are increasingly appreciated, the plasmalemmal nanodomains are by far the best studied, in part because they are more readily accessible. The lateral segregation within the plasma membrane is caused by a variety of lipid-lipid, lipid-protein, and protein-protein associations, as well as by interactions of membrane components with the cytoskeleton.2 The net result of these interactions is the nonrandom distribution of lipids and proteins across different types of nanodomains. One important function ascribed to these structures is the concentration of proteins or lipids to generate transport stations or signaling complexes (signalosomes). Examples of such nanodomains are the lateral assemblies of cholesterol and sphingolipids, which are termed lipid rafts,1,10,11 as well as caveolae and clathrin-coated pits.12
