Sorting of GPI-anchored proteins from yeast to mammals--common pathways at different sites?

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are luminal secretory cargos that are attached by a post-translational glycolipid modification, the GPI anchor, to the external leaflet of the plasma membrane. GPI-APs are conserved among eukaryotes and possess many diverse and vital functions for which the GPI membrane attachment appears to be essential. The presence of the GPI anchor and its subsequent modifications along the secretory pathway confer to the anchored proteins unique trafficking properties that make GPI-APs an exceptional system to study mechanisms of sorting. In this Commentary, we discuss the recent advances in the field of GPI-AP sorting focusing on the mechanisms operating at the level of the exit from the ER and from the trans-Golgi network (TGN), which take place, respectively, in yeast and in polarized mammalian cells. By considering the similarities and differences between these two sorting events, we present unifying principles that appear to work at different sorting stations and in different organisms.