Using Sterol Substitution to Probe the Role of Membrane Domains in Membrane Functions

Ordered membrane lipid domains rich in sphingolipids and sterols ("lipid rafts") are thought to be important in many biological processes. However, it is often difficult to distinguish domain-dependent biological functions from ones that have a specific dependence on sterol, e.g. are dependent upon a protein with a function that is dependent upon its binding to sterol. Removing cholesterol and replacing it with various sterols with varying abilities to form membrane domains or otherwise alter membrane properties has the potential to help distinguish these cases. This review describes this strategy, and how it has been applied by various investigators to understand cellular functions.