Lipid raft proteomics: more than just detergent-resistant membranes

The fluid mosaic model of membrane bilayers implies that proteins and lipids are homogenously distributed in the 2D surface of a membrane. Numerous lines of biochemical, biophysical and optical evidence now suggest that organized sub-domains of membranes exist, a subset of which are known as lipid rafts. Rafts are enriched in cholesterol, saturated phospholipids, sphingolipids and what is thought to be a specific subset of proteins. Biologically rafts have been implicated in several fundamental processes, including signal transduction, bacterial invasion, apical/basolateral sorting in polarized cells and viral budding; therefore, defining the raft proteome is an attractive goal. Rafts can be enriched biochemically by taking advantage of their buoyant density and resistance to non-ionic detergents so numerous studies have used a fraction so enriched as a starting point for characterizing the proteome of lipid rafts. This review will focus on approaches to lipid raft proteomics with a specific emphasis on the use of quantitative methods to ensure the specificity and/or functionality of raft proteins.