The Glycosylphosphatidylinositol Anchor: A Complex Membrane-Anchoring Structure for Proteins

Abstract

Positioned at the C-terminus of many eukaryotic proteins, the glycosylphosphatidylinositol (GPI) anchor is a posttranslational modification that anchors the modified protein in the outer leaflet of the cell membrane. The GPI anchor is a complex structure comprising a phosphoethanolamine linker, glycan core, and phospholipid tail. GPI-anchored proteins are structurally and functionally diverse and play vital roles in numerous biological processes. While several GPI-anchored proteins have been characterized, the biological functions of the GPI anchor have yet to be elucidated at a molecular level. This review discusses the structural diversity of the GPI anchor and its putative cellular functions, including involvement in lipid raft partitioning, signal transduction, targeting to the apical membrane, and prion disease pathogenesis. We specifically highlight studies in which chemically synthesized GPI anchors and analogues have been employed to study the roles of this unique posttranslational modification.

Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner

“…GPI anchors represent a structurally diverse class of posttranslational modifications that anchor proteins in the outer leaflet of the cellular membrane and are involved in a number of functions, including protein trafficking into lipid rafts, signal transduction, cellular communication, targeting of protein to apical membranes, and others (35,44). It is believed that GPIcontaining proteins are sorted toward glycosphingolipid-and cholesterol-rich rafts, a sorting that already occurs in the Golgi (34).…”

Plasma Membrane Localization of Solanum tuberosum Remorin from Group 1, Homolog 3 Is Mediated by Conformational Changes in a Novel C-Terminal Anchor and Required for the Restriction of Potato Virus X Movement

“…In plants, these include N-myristoylation, S-palmitoylation, prenylation by farnesyl or geranylgeranyl moieties, or attachment of glycosylphosphatidylinositol (GPI) anchors (Thompson and Okuyama, 2000). GPI anchors, for example, tightly associate proteins to the extracellular face of PMs by interaction of the inositol head group of the membrane lipid phosphatidylinositol with a glucosamine residue linked to the C-terminal amino acid of the protein (Paulick and Bertozzi, 2008). As an alternative mechanism, globular structures either recognize phospholipids in a stereospecific manner or associate with membranes by their biophysical properties (for review, see Lemmon, 2008).…”

The dendritic cell life cycle

“…Cholesterol depletion and src kinase inhibition inhibit Ca 2+ mobilization, while src kinases are not required for TNFα production. 19 As it is commonly accepted that GPIanchored proteins associate with lipid rafts and that src kinases concentrate in these microdomains, 55 these data suggest that CD14 directly induces Ca 2+ mobilization and NFAT activation due to its localization in lipid rafts, which is mediated by the GPI anchor, and through the action of src kinases.…”