GPIanchors

Abstract

Many proteins are attached to the outer surface of the membrane by a glycosyl‐phosphatidylinositol (GPI) anchor covalently linked to the C‐terminal amino acid. All GPI anchors have the core structure “ethanolamine‐PO 4 ‐6Manα1‐2Manα1‐6Manα1‐4GlcNH 2 α1‐6 myo ‐inositol‐1‐PO 4 ‐lipid” but vary in the nature of the lipid moiety and in side‐chain modifications to the core glycan ( see Glycosylphosphatidylinositol anchors‐ a structural perspective ). The GPI anchor is built up by sequential addition of sugars and ethanolamine phosphate to phosphatidylinositol and then transferred by a transamidase enzyme to the protein. Proteins destined to be GPI anchored have an N‐terminal signal peptide for translocation into the lumen of the endoplasmic reticulum and a C‐terminal signal that directs addition of the GPI anchor. Experimentally, the presence of a GPI anchor can be determined by digestion with bacterial phosphatidylinositol‐specific phospholipase C, detection of the cross‐reacting determinant, metabolic labeling with components of the anchor, or relative detergent insolubility. In addition to the stable association of a protein with the membrane, GPI anchors convey other properties on proteins including susceptibility to cleavage by phospholipases, association with detergent‐insoluble lipid rafts, intracellular targeting, transmembrane signaling, endocytosis via caveolae, and intercellular transfer.