Tracking down lipid flippases and their biological functions

The various organellar membranes of eukaryotic cells display striking differences in the composition, leaflet distribution and transbilayer movement of their lipids. In membranes such as the endoplasmic reticulum, phospholipids can move readily across the bilayer, aided by membrane proteins that facilitate a passive equilibration of lipids between both membrane halves. In the plasma membrane, and probably also in the late Golgi and endosomal compartments, flip-flop of phospholipids is constrained and subject to a dynamic, ATP-dependent regulation that involves members of distinct protein families. Recent studies in yeast, parasites such as Leishmania, and mammalian cells have identified several candidates for lipid flippases, and whereas some of these serve a fundamental role in the release of lipids from cells, others appear to have unexpected and important functions in vesicular traffic: their activities are required to support vesicle formation in the secretory and endocytic pathways.