Membrane Domains and the Lipid Raft Concept

Abstract

The bulk structure of biological membranes consists of a bilayer of amphipathic lipids. According to the fluid mosaic model proposed by Singer and Nicholson, the glycerophospholipid bilayer is a two-dimensional fluid construct that allows the lateral movement of membrane components. Different types of lateral interactions among membrane components can take place, giving rise to multiple levels of lateral order that lead to highly organized structures. Early observations suggested that some of the lipid components of biological membranes may play active roles in the creation of these levels of order. In the late 1980s, a diverse series of experimental findings collectively gave rise to the lipid raft hypothesis. Lipid rafts were originally defined as membrane domains, i.e., ordered structures created as a consequence of the lateral segregation of sphingolipids and differing from the surrounding membrane in their molecular composition and properties. This definition was subsequently modified to introduce the notion that lipid rafts correspond to membrane areas stabilized by the presence of cholesterol within a liquid-ordered phase. During the past two decades, the concept of lipid rafts has become extremely popular among cell biologists, and these structures have been suggested to be involved in a great variety of cellular functions and biological events. During the same period, however, some groups presented experimental evidence that appeared to contradict the basic tenets that underlie the lipid raft concept. The concept is currently being redefined , with greater consistency regarding the true nature and role of lipid rafts. In this article we will review the concepts, criticisms, and the novel confirmatory findings relating to the lipid raft hypothesis.

Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis

“…). Another type of cholesterol domain attracting great interest albeit with some controversy is lipid rafts (Head et al ., ; Sonnino and Prinetti ). Lipid rafts are thought to be scaffolds for interactions of proteins and lipids.…”

“…, ; Schroeder et al . ; Sonnino and Prinetti ). Data from animal and cell culture studies have shown that large changes can occur in membrane cholesterol domains that take place in the absence or minimal changes in total cholesterol levels.…”

Raft-like membranes from the trans-Golgi network and endosomal compartments

“…These early experiments were controversial in terms of their interpretation and use, but they nevertheless laid the foundations for many current ideas on membrane organization and, in particular, the lipid raft hypothesis 13,[75][76][77][78] . Notably, although previous protocols generally included a cell disruption step followed by a selective extraction treatment to dissolve away or selectively remove non-raft membrane fragments, they did not incorporate preclearance steps to distinguish between lipid raft microdomains present at the plasma membrane and those at other subcellular sites, such as the TGN and late endosomes 79 .…”

Discovering cellular protein‐protein interactions: Technological strategies and opportunities

“…A particularly interesting application of EMARS is the research of lipid rafts, where the HRP is coupled to cholera toxin which binds a ganglioside specific for these membrane domains . Lipid rafts have a distinct composition and are generally difficult to research with other methods, but they are essential to many cellular processes and can have sizes within the range of EMARS …”