Secrets of caveolae- and lipid raft-mediated endocytosis revealed by mammalian viruses

In recent years, it has been unambiguously shown that caveolae and lipid rafts can internalize cargo upon stimulation by multivalent ligands, demonstrated by the infectious entry routes of certain non-enveloped viruses that bind integrins or glycosphingolipids. We currently understand little about the membrane trafficking principles of this endocytic route, but it is clear that we cannot use paradigms from classical membrane traffic. Recent evidence indicates that caveolae- and lipid raft-mediated endocytosis plays important roles in cell adhesion and anchorage-dependent cell growth, but the underlying mechanisms are not known. In this review, I will introduce new models based on current research that aims at identifying the core machinery, regulatory components and design principles of this endocytic route in order to understand its role in cellular physiology. Again, viruses are proving to be excellent tools to reach that goal.