Lipid Rafts As a Membrane-Organizing Principle

Abstract

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 based on 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 for sphingolipid-cholesterol self-assembly with protein specificity to selectively focus membrane bioactivity.

The lateral compartmentation of the yeast plasma membrane

“…The membrane domains are thought to be created by spontaneous lipid-phase separation. Specific lipids (sterols, sphingolipids with long saturated fatty acids) condense into so-called 'lipid rafts' [15], small areas of liquid-ordered (l o ) phase, which are excluded from the surrounding membrane in a liquid-disordered (l d ) phase. Such a membrane compartmentation has clearly been demonstrated in artificial membranes [2].…”

Stress‐induced host membrane remodeling protects from infection by non‐motile bacterial pathogens

“…Membrane rafts, which are highly dynamic membrane domains enriched in sphingolipids and cholesterol that mediate the compartmentalization of signaling proteins and receptors (Lingwood & Simons, 2010; Sezgin et al , 2017), have been shown to be utilized by numerous bacterial pathogens (reviewed in Refs: Lafont & van der Goot, 2005; Bagam et al , 2017). For example, Shigella uses its IpaB effector protein to bind the host raft‐associated CD44 transmembrane receptor (Lafont et al , 2002); entry of Listeria monocytogenes into host cells requires the localization of the host receptors E‐cadherin and HGF‐R/Met in specific lipid domains (Seveau et al , 2004).…”

Specific adhesion of membranes simultaneously supports dual heterogeneities in lipids and proteins

“…Heterogeneities in the lipid and protein composition of the membrane are often associated with adhesion sites; these heterogeneities are frequently known as ''rafts'' and are thought to facilitate signalling by clustering together proteins with an affinity for the liquid-ordered lipid phase that characterizes the raft. [1][2][3][4][5][6] To elucidate the biophysical principles undergirding raft formation, experimental physical scientists have often used simplified experimental model systems in the form of giant unilamellar vesicles (GUVs) that are typically made of a high-melting lipid, a low-melting lipid, and a sterol. Such biophysical studies have largely focused on lipid phase separation at thermodynamic equilibrium, [7][8][9][10][11][12][13] and on the effects of biologically-relevant perturbations such as tension 12,13 and curvature and undulations.…”