Modulation of membrane lipid raft by omega-3 fatty acids and possible functional implication in receptor tyrosine-kinase activation

Abstract

Current understanding of biologic membrane structure and function is largely based on the concept of lipid rafts. Lipid rafts are composed primarily of tightly packed, liquid-ordered sphingolipids/cholesterol/saturated phospholipids that float in a sea of more unsaturated and loosely packed, liquid-disordered lipids. Lipid rafts have important clinical implications because many important membrane-signalling proteins are located within the raft regions of the membrane, and alterations in the raft structure can alter the activity of these signalling proteins. Because rafts are lipid-based, their composition, structure, and function are susceptible to manipulation by dietary components such as omega-3 polyunsaturated fatty acids and by cholesterol depletion. Important components of lipid rafts are receptor tyrosine-kinase, such as the ErbB receptor superfamily. Here we review how alteration of raft lipids affects the raft/nonraft localization and hence the function of several proteins involved in cell signalling, focusing our discussion on two members of the ErbB receptors: EGFR and ErbB2, that are specifically involved in the development of many solid tumors, such as mammary adenocarcinomas.