Lipid Raft - Controversy About Lipid Rafts

Controversy About Lipid Rafts

The role of rafts in cellular signaling, trafficking, and structure has yet to be determined despite many experiments involving several different methods, and their very existence is controversial despite all the above.

Arguments against the existence of lipid rafts include the following:

• First, a line tension should exist between the Lα and Lo phases. This line has been seen in model membranes, but has not been readily observed in cell systems.

• Second, there is no consensus on lipid raft size, which has been reported anywhere between 1 and 1,000 nanometres.

• Third, the time scale of lipid raft existence is unknown. If lipid rafts exist, they may only occur on a time scale that is irrelevant to biological processes.

• Fourth, the entire membrane may exist in the Lo phase.

A first rebuttal to this point suggests that the Lo phase of the rafts is more tightly packed due to the intermolecular hydrogen bonding exhibited between sphingolipids and cholesterol that is not seen elsewhere.

A second argument questions the effectiveness of the experimental design when disrupting lipid rafts. Pike and Miller discuss potential pitfalls of using cholesterol depletion to determine lipid raft function. They noted that most researchers were using acute methods of cholesterol depletion, which disrupt the rafts, but also disrupt another lipid known as PI(4,5)P₂. PI(4,5)P₂ plays a large role in regulating the cell’s cytoskeleton, and disrupting PI(4,5)P₂ causes many of the same results as this type of cholesterol depletion, including lateral diffusion of the proteins in the membrane. Because the methods disrupt both rafts and PI(4,5)P₂, Kwik et al. concluded that loss of a particular cellular function after cholesterol depletion cannot necessarily be attributed solely to lipid raft disruption, as other processes independent of rafts may also be affected. Finally, while lipid rafts are believed to be connected in some way to proteins, Edidin argues that proteins attract the lipids in the raft by interactions of proteins with the acyl chains on the lipids, and not the other way around.