Membrane rafts, or lipid rafts, are microdomains of the plasma membrane enriched in cholesterol and sphingolipids, and play an important role in regulation of apoptosis. The structure of membrane rafts is dynamic, resulting in an ever-changing content of both lipids and proteins. Cholesterol, a major component of membrane rafts, is critical for the formation and configuration of membrane 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 membrane raft disruption and activate or deactivate raft-associated proteins, such as death receptor proteins, protein kinases, and calcium channels.
This study focuses on the role of membrane rafts of HaCaT keratinocytes in ultraviolet light (UV)-induced apoptosis. HaCaT keratinocytes readily undergoes apoptosis upon exposure to UV light mediated by association of clustered membrane rafts with the activated Fas death receptor. This study demonstrates the cholesterol dependence of UV-induced Fas activation and apoptosis in HaCaT cells. At one hour following 50 mJ/cm2 ultraviolet B (UVB) irradiation, raft cholesterol levels are increased while raft ceramide levels are decreased, Fas receptor activation occurs in the membrane rafts, and apoptotic PARP cleavage is evident. Decreased amounts of the Fas-recruited apoptotic Daxx protein following UVB irradiation suggests that the apoptotic caspase cascade pathway is more important in the initiation on UV-induced apoptosis than the alternative JNK pathway in HaCaT cells. The proposed mechanism by which membrane raft clustering causes Fas activation provides clues to understanding the role of membrane raft clustering in other cellular signaling processes.