Structural Determinants and Functional Consequences of Protein Partitioning to Membrane Domains
The organization of metazoan membranes into functional domains is a key feature of their physiology. A subset of these domains, known as membrane rafts, has been implicated in a large variety of processes occurring at the plasma membrane. However, the molecular mechanisms by which raft domains regulate cell function remain elusive. Here, we demonstrate that membrane raft association is a necessary and sufficient sorting signal for cell surface localization of integral membrane proteins, and that this raft association is governed by the properties of the protein transmembrane domain. These results begin to define the physical bases for protein raft affinity and establish lateral domain formation in membranes as a mechanism for biosynthetic sorting in mammalian cells.