Glycosyl-phosphatidylinositol (GPI)-anchored proteins are found predominantly at the apical surface of polarized epithelial cells. As the GPI anchor has a natural affinity for sphingolipid–cholesterol rafts, it has been widely assumed that this association represents the relevant sorting event responsible for transport to the apical domain.
Benting et al. (page 313) contradict this assumption and report that the sorting is mediated by N-glycans. They use rat growth hormone (rGH) as a test protein, and find that 60% of a GPI-anchored version is sorted to the basolateral side. Association with rafts does not necessarily result in apical sorting, as the protein is raft associated on both apical and basolateral sides. With the addition of one or two sites for N-glycosylation to the GPI-anchored rGH, the distribution of the protein shifts to 60% apical.
The new rule for protein sorting may...
