Analysis of the Cell-Surface Distribution of GPI-Anchored Proteins

Abstract

Many cell-surface eukaryotic proteins, including several receptors, enzymes, and adhesion molecules, have a glycolipid modification at their carboxy-terminal end (Fig. 1 A). This is a posttranslational modification that serves as a membrane anchor and involves the replacement of the carboxy-terminal peptide sequence of the protein by a glycosylphosphatidylinositol (GPI) moiety (1,2). The structure and biosynthesis of the GPI moiety are now well understood (1–4). In spite of the extensive biochemical information on the GPI moiety of GPI-anchored proteins, the functions of this ubiquitous protein modification are less understood, although it has been implicated in a variety of cell biological processes (5). The GPI anchor has been proposed to act as an apical targeting signal for proteins in some epithelial cell types via its association with putative glycolipid rafts in the trans-Golgi network (6,7). GPI-anchoring has also been shown to be important for the intracellular signaling capacity of several proteins, especially in lymphocytes. In most cases, the crosslinking of the protein is a prerequisite for their signaling function (8,9).