Rafting trips into the cell: Membrane domains in MHC internalization

Lipid rafts are small, heterogeneous and short-lived assemblies of cholesterol, sphingolipids and few proteins in biological membranes. They can be converted to larger and more permanent membrane domains by coalescence. Cells appear to be able to modulate the size and the longevity of lipid rafts and thus exploit the local enrichment of membrane components for processes ranging from signaling to intracellular sorting and transport. In a recent paper, we provided evidence for the internalization of MHC I and MHC II along two distinct endocytosis pathways in mouse B-lymphocytes. Both pathways were much more dependent on membrane cholesterol than the clathrin-mediated uptake of transferrin receptor, which implicated lipid rafts in the internalization of MHC molecules. Indeed, MHC I and MHC II prefer distinct raft-like membrane environments as revealed by a co-clustering analysis with the sphingolipids GM1 and GM2. Moreover, MHC I and MHC II distributed to different types of detergent resistant membranes (DRMs) prepared by a novel detergent extraction procedure. In this article addendum we discuss the relationship between DRMs, small lipid rafts and stabilized rafts/membrane domains and propose a role for membrane domains in the endocytosis of MHC proteins.