Lipid raft: A floating island of death or survival

Abstract

Lipid rafts are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in the initiation of many pharmacological agent-induced signaling pathways and toxicological effects. The structure of lipid rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, as a major component of lipid rafts, is critical for the formation and configuration of lipid raft microdomains, which provide signaling platforms capable of activating both pro-apoptotic and anti-apoptotic signaling pathways. A change of cholesterol level can result in lipid raft disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels. Several anti-cancer drugs are able to suppress growth and induce apoptosis of tumor cells through alteration of lipid raft contents via disrupting lipid raft integrity.

Figure 1

Apoptotic pathways mediated by lipid rafts involving protein kinase activation or deactivation, apoptotic membrane receptor activation, or increased intracellular calcium levels

Figure 2

Mechanism of activation of receptors, kinases, and calcium channels within lipid rafts of cells: (a) activated molecules may residually be located in lipid rafts, (b) molecules may translocate into lipid rafts upon activation, (c) smaller lipid rafts may combine to form larger lipid rafts containing activated molecules