Transbilayer phospholipid movement facilitates annexin 2 translocation across membranes
Annexins are cytosolic phospholipid binding proteins that can be found on the outer leaflet of the plasma membrane. Extracellular annexin functions include fibrinolysis activity and cell migration, among other functions. Despite having well described extracellular functions, the mechanism of annexin transport from the cytoplasmic inner leaflet to the extracellular outer leaflet of the plasma membrane remains unclear. Here, we show that the transbilayer movement of phospholipids facilitates the transport of annexins A2 and A5 across membranes in cells and in liposomes. We identified TMEM16F (anoctamin-6) as a lipid scramblase required for transport of these annexins to the outer leaflet of the plasma membrane. This work reveals a mechanism for annexin translocation across membranes which depends on plasma membrane phospholipid remodelling.
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/1)
Biotechnology and Biological Sciences Research Council (BB/P010911/1)
Medical Research Council (MC_UU_12012/5)