Membrane curvature sorts lipids

Abstract

The enrichment of sphingolipids and cholesterol in the mammalian plasma membrane, and unsaturated phosphatidylcholine (PC) in the endoplasmic reticulum, requires lipid sorting in the Golgi apparatus. Most sphingolipids are synthesized in the Golgi lumen (Holthuis & Levine, 2005). Therefore, unsaturated PC must be segregated from sphingolipids and cholesterol, and selectively included in retrograde carrier vesicles (van Meer, 1989). Lipid‐phase separations into a fluid liquid‐crystalline phase and a solid‐gel phase were characterized in the 1970s, but mammalian membranes are always fluid: membranes similar to the endoplasmic reticulum contain unsaturated lipids, whereas the saturated lipids in plasma membranes are ‘fluidized’ by cholesterol. In the 1980s, PC–cholesterol mixtures were found to display fluid–fluid immiscibility, which yielded a liquid‐disordered (ld) phase and a less‐fluid liquid‐ordered (lo) phase. Since then, ternary phase diagrams have shown that sphingomyelin (SM)/cholesterol/PC mixtures, which mimic the non‐cytosolic leaflet of Golgi and plasma membranes, segregate into ld and lo phases, with the latter being enriched in SM and cholesterol (Simons & Vaz, 2004). Although this could explain lipid segregation, lipid sorting requires the selective incorporation of one of the two phases into a transport carrier with a specific destination. Interestingly, in model membranes, the phases bud away from each other (Baumgart et al , 2003). However, when no external force is applied, they do so on a micrometer scale compared with the typical 40–70 nm size of cellular transport vesicles. A new study has shown that the induction of a curvature that is typical of …