Lipid polarity and sorting in epithelial cells

The plasma membrane is of vital importance to the cell, because it protects the cytoplasmic space and because the surface proteins and lipids determine the interactions of the cell with the environment. Epithelial cells are especially interesting in this sense, because their plasma membranes consist of two domains that face two different environments. In addition to the transbilayer heterogeneity in the epithelial cells, the plasma membrane contains two specialized domains in the plane of the lipid bilayer. The apical plasma membrane domain faces the external environment, whereas the opposing basolateral domain interacts with the neighboring cells and the underlying tissue. The common precursor for sphingolipid biosynthesis, ceramide, is made in the endoplasmic reticulum (ER). The biosynthesis of sphingomyelin (SM) has been assigned to the cis-Golgi from colocalization with cis- and not with trans-Golgi markers after cell fractionation. The active site of SM synthase and its products have been found to reside in the luminal exoplasmic leaflet. An interesting possibility is that SM is sorted in the cis-Golgi into the outgoing pathway, by clustering into sphingolipid microdomains, separating the sphingolipids from the glycerolipids. This cis-Golgi sphingolipid sorting event could be the more general case of glycosphingolipid, sorting in the trans-Golgi network (TGN) of the epithelial cells, with possible important implications for the transport of newly synthesized cholesterol from the ER to the cell surface.