Flippases and scramblases in the plasma membrane

Phospholipids in the plasma membrane of eukaryotic cells are asymmetrically distributed between the outer and inner leaflets.1 Phosphatidylcholine and sphingomyelin are located primarily in the outer leaflet, while phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEtn) are restricted to the cytoplasmic side. This asymmetrical phospholipid distribution is disrupted during various biological processes. PtdSer exposed on the outside of activated platelets promotes blood clotting, and on apoptotic cells acts as an “eat me” signal for macrophages. The phospholipid distribution is regulated by lipid transporters in the plasma membrane.1 Scramblases non-specifically and bidirectionally transport phospholipids between the inner and outer leaflets in an ATP-independent manner, while flippases, also known as ATP-dependent aminophospholipid translocases, transport PtdSer and PtdEtn from the extracellular to the cytoplasmic side.1