Plasma membrane organization and function: moving past lipid rafts

Abstract

"Lipid raft" is the name given to the tiny, dynamic, and ordered domains of cholesterol and sphingolipids that are hypothesized to exist in the plasma membranes of eukaryotic cells. According to the lipid raft hypothesis, these cholesterol- and sphingolipid-enriched domains modulate the protein-protein interactions that are essential for cellular function. Indeed, many studies have shown that cellular levels of cholesterol and sphingolipids influence plasma membrane organization, cell signaling, and other important biological processes. Despite 15 years of research and the application of highly advanced imaging techniques, data that unambiguously demonstrate the existence of lipid rafts in mammalian cells are still lacking. This Perspective summarizes the results that challenge the lipid raft hypothesis and discusses alternative hypothetical models of plasma membrane organization and lipid-mediated cellular function.

FIGURE 1:

Hypothetical model in which the plasma membrane is compartmentalized by a network of transmembrane proteins (orange) that interact with the underlying cytoskeleton and obstruct the lateral diffusion of free transmembrane proteins (yellow), GPI-anchored proteins (green and red), and lipids. In this model, compositionally distinct domains may result from the association of the cytoskeleton with membrane components. Alternatively, the diffusion barrier established by the cytoskeleton and its associated proteins may maintain the concentration gradients produced by vesicle traffic.