Exploration of the functional proteome: lessons from lipid rafts

Lipid rafts are liquid-ordered cholesterol and glycolipid-enriched membrane microdomains that act as sorting devices for the accumulation of acylated signaling molecules. Lipid rafts are implicated in receptor signaling, protein and membrane trafficking, cytoskeletal re-organization and the entry of infectious organisms into cells. Several recent studies have investigated the composition of the lipid raft proteome by mass spectrometry. Here, those studies and the insights they afford into raft function are reviewed. Lipid rafts contain hydrophobic proteins, posing problems of isolation, recovery and analysis. Recent advances in proteome preparation that extend the boundaries of protein detection in lipid rafts are described and their implications for the exploration of the functional proteome are discussed.