Lipid-driven sorting and fission

JCB • VOLUME 169 • NUMBER 2 • 2005 214 Lipid-driven sorting and fission hanges in membrane shape during trafficking require proteins, and those proteins are thought to operate mechanically to extrude or squeeze membranes. But biological membranes are also thought to be poised near a phase transition between liquidordered (L o ) and liquid-disordered (L d ) states. Aurélien Roux, Patricia Bassereau, Bruno Goud (Institut Curie, Paris, France), and colleagues now report that in vitro tube formation is favored from L d domains, and phase separation induces fission. Proteins that affect lipid distributions in vivo may thus favor or disfavor tubulation and fission events during protein trafficking. The preferential tubulation from L d domains makes sense, as reduced interactions between lipid head groups make these domains more easily deformable. The French team used biotinylated lipids and kinesin-laden beads to pull tubes out of lipid vesicles in vitro. More tubes were pulled from L d domains. But even in vesicles lacking visible segregation between L d and L o domains, the pulled tubes are enriched in lipids from the L d phase because the other lipids sort out of the tubes. For some lipid compositions such a sorting event promotes phase separation in tubes. In vitro, the induction of phase separation (via photooxidation of cholesterol) induced fission; in many cases this clearly occurred at an L o /L d boundary. If this holds up in vivo, those interested in trafficking may have to think about lipid dynamics as much as protein mechanics. Membrane fission proteins have been thought of as motors driving a constriction event, but “the main function of these proteins,” says Goud, “might be to help promote this phase transition.”