GPI-Anchored Proteins in Health and Disease
Covalently linked to the C-terminus of many proteins, the glycosyl-phosphatidylinositol (GPI) anchor provides a means to anchor the attached protein to the cell membrane. Whilst the GPI anchor of mature proteins may be extensively modified, all GPI anchors possess a common core structure comprising of a phosphoethanolamine linker and a phosphatidylinositol lipid tail, separated by a glycan core. GPI-anchored proteins have been demonstrated to perform diverse physiological functions; however, the GPI anchor itself imparts certain properties on the protein. These include association with detergent-insoluble lipid rafts, targeting to the apical membrane of polarised cells and signal transduction. In addition to their normal functions, GPI-anchored proteins have been shown to play roles in the pathogenesis of disease. In this chapter we discuss the structure of the GPI anchor and its putative physiological functions, as well as discussing its contribution to the diseases paroxysmal nocturnal hemoglobinuria, prion disease and malaria, as well as bacterial infections.
KeywordsLipid Raft Prion Disease Bovine Spongiform Encephalopathy Neural Cell Adhesion Molecule Paroxysmal Nocturnal Hemoglobinuria
- Brodsky, R.A. (2006). New insights into paroxysmal nocturnal hemoglobinuria. Hematology Am. Soc. Hematol. Educ. Program 24–28:516.Google Scholar
- Eisenhaber, B., Schneider, G., Wildpaner, M., et al. (2004). A sensitive predictor for potential GPI lipid modification sites in fungal protein sequences and its application to genome-wide studies for Aspergillus nidulans, Candida albicans, Neurospora crassa, Saccharomyces cerevisiae and Schizosaccharomyces pombe. J. Mol. Biol. 337:243–253.PubMedCrossRefGoogle Scholar
- Fukushima, K., Ikehara, Y., Kanai, M., et al. (2003). A beta-N-acetylglucosaminyl phosphate diester residue is attached to the glycosylphosphatidylinositol anchor of human placental alkaline phosphatase: a target of the channel-forming toxin aerolysin. J. Biol. Chem. 278:36296–36303.PubMedCrossRefGoogle Scholar
- Schofield, L., Novakovic, S., Gerold, P., et al. (1996). Glycosylphosphatidylinositol toxin of Plasmodium up-regulates intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression in vascular endothelial cells and increases leukocyte and parasite cytoadherence via tyrosine kinase-dependent signal transduction. J. Immunol. 156:1886–1896.PubMedGoogle Scholar