In eukaryotic cells, a subset of proteins are attached to the external leaf
let of the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor.
There is substantial evidence suggesting that these GPI-anchored proteins a
re clustered in sphingolipid-sterol microdomains or rafts. Since the precur
sors of these microdomain components are synthesized mainly in the endoplas
mic reticulum, it is possible that microdomain assembly occurs during trans
port along the exocytic route. A sorting mechanism for GPI-anchored protein
s using sphingolipid microdomains as selective platforms for vesicle buddin
g has been proposed to operate at different steps in the secretory pathway.
Here, we discuss this sorting model in the context of the data obtained fr
om different biological and artificial systems, in addition to other partic
ularities of the intracellular transport of the GPI-anchored proteins.