Integrins and Urokinase Receptors Show Distinct Mechanisms of Protein Sequestration in Raft-Mimicking Lipid Mixtures: Influence of Bilayer Asymmetry, Ligand Binding, and Cholesterol Content

Abstract

Lipid heterogeneities, such as lipid rafts, are widely considered to be important for the functionality of membrane proteins by causing protein sequestration. However, the underlying mechanisms of such sequestration processes remain elusive, in part, due to the often small size and transient nature of functional membrane heterogeneities in cellular membranes. Recently, we introduced a powerful model membrane platform that allows the thorough analysis of membrane protein sequestering and oligomerization in well-defined heterogeneous lipid environments in the absence of artificial crosslinking agents using single molecule-sensitive confocal fluorescence intensity analysis paired with a photon counting histogram (PCH) method (1). By comparing the sequestration behavior of integrins (αvβ3 and α5β1) and urokinase receptors in such a model membrane platform, here we provide insight into the potentially distinct mechanisms of protein sequestration of transmembrane and GPI-anchored proteins in biological membranes. Specifically, the distinct protein sequestration behavior of both types of membrane proteins is illustrated in terms of bilayer asymmetry, ligand binding, and bilayer cholesterol content.Reference(1) Siegel, A. P. et al. (2011) Biophys J 101(7): 1642–1650.