Polarized sorting of GPI proteins

The asymmetric distribution of proteins and lipids in two distinct domains of the plasma membrane (PM) of polarized epithelial cells is accomplished by continuous sorting of newly synthesized components and their regulated internalization. Here we discuss the mechanisms of apical sorting of glycosylphosphatidilinositol-anchored proteins (GPI-APs) especially focusing on their biosynthetic pathway. Recent evidences indicate that this event depends on both association to specialized lipid domains (rafts) and clustering in high-molecular-weight complexes at the level of the Golgi apparatus. We discuss the evidences present in literature pointing toward the involvement of the protein ectodomain, the GPI anchor, the lipid environment, and the presence of a putative receptor in this process. We also examine the role of the cytoskeleton and other molecular components of the exocytic pathway in post-TGN transport of GPI-APs to the PM.