Glycosylphosphatidylinositol (GPI) anchors appear to confer unique biophysical properties on the
proteins to which they are covalently linked. Model membrane systems provide a powerful tool to explore the
effects of bilayer properties on the behaviour of GPI-anchored proteins. Such studies have typically been carried
out after reconstitution/insertion of purified GPI-anchored proteins into symmetric or asymmetric lipid bilayer
vesicles, supported lipid bilayers, or lipid monolayers. Biophysical studies using atomic force microscopy and
Langmuir isotherms have revealed quantitative details of the interactions between GPI-anchored proteins and
model membranes. Proteins carrying GPI anchors are believed to be targeted to detergent-resistant cholesterol/
sphingolipid-rich lipid rafts in both intact cells and model membranes, and the special properties of these
microenvironments may also modulate their functional activity. GPI-anchored proteins are likely closely
associated with the bilayer surface, so that the biophysical properties of the membrane, including curvature and
lipid fluidity, modulate their conformation and activity. The GPI anchor can be cleaved by both endogenous and
exogenous phosphatidylinositol (PI)-specific phospholipases C and D, from sources such as bacteria, protozoa
and mammalian tissues. The release of GPI-anchored proteins in soluble form by phospholipases may play a key
role in regulating their surface expression and activity. The GPI anchor appears to impose structural restraints,
and its removal may alter the conformation, antigenicity and enzymatic activity of the protein. PI-specific
phospholipases must interact closely with the membrane surface to cleave GPI anchors, and their activity is also
greatly influenced by membrane biophysical properties.
