Role of anionic lipids in endocytosis

The anionic lipids phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P₂] and phosphatidylserine (PtdSer) localise to the cytosolic leaflet of the plasma membrane, where endocytic sites form, and are thought to have important roles in clathrin-mediated endocytosis (CME). However, how they function during the distinct stages of CME is unknown. On page 6157, Yidi Sun and David Drubin set out to investigate the role of PtdIns(4,5)P₂ and PtdSer in the initiation of CME and vesicle formation in Saccharomyces cerevisiae using live-cell imaging of endocytic actin patch dynamics in yeast mutants with altered plasma membrane and internal membrane lipid composition. Their analysis of a mss4 mutant, which has severely reduced levels of PtdIns(4,5)P₂, revealed that PtdIns(4,5)P₂ is required for invagination of the endocytic membrane but is less important for initiation of the endocytic site. Furthermore, analysis of mutants of the endosome-to-Golgi transport pathway showed that endocytic proteins not only assemble on the plasma membrane but also on intracellular membrane compartments, and that PtdSer localises to both. In cells lacking Cho1p, a key enzyme for PtdSer synthesis, the authors found the establishment of a polarised endocytic patch to be defective, indicating that PtdSer is involved in directing endocytic proteins to the membrane, thus providing further insight into endocytic internalisation events.