Glycosylphosphatidylinositol-anchored proteins (GPI-anchored proteins) (GPI-APs)

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are a diverse class of cell-surface proteins that are covalently attached to the plasma membrane via a complex glycolipid anchor [1]. This post-translational modification occurs in the endoplasmic reticulum and is essential for the stable expression and functional localization of over 150 different proteins in humans, including enzymes, receptors, and adhesion molecules [2]. GPI-APs play critical roles in signal transduction, immune regulation, and apical sorting in polarized cells [3]. Deficiencies in the GPI biosynthesis pathway, such as those caused by somatic mutations in the PIGA gene, lead to Paroxysmal Nocturnal Hemoglobinuria (PNH), where the loss of GPI-anchored complement regulators CD55 and CD59 results in chronic intravascular hemolysis [4]. Additionally, GPI-APs serve as receptors for various bacterial toxins and are involved in the pathogenesis of prion diseases [5]. Therapeutic strategies targeting this class include complement inhibitors to manage PNH symptoms and novel antifungal agents, such as manogepix, which selectively inhibit the fungal GPI biosynthesis pathway [6]. Sources: [1] Kinoshita T. (2020). Biosynthesis and biology of mammalian GPI-anchored proteins. Gene. [2] Ferguson M.A.J., et al. (2015). Glycosylphosphatidylinositol Anchors. Essentials of Glycobiology. [3] Paulick M.G., Bertozzi C.R. (2008). The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure. Biochemistry. [4] Brodsky R.A. (2014). Paroxysmal nocturnal hemoglobinuria. Blood. [5] Taylor D.R., Hooper N.M. (2006). The prion protein and lipid rafts. Molecular Membrane Biology. [6] Miyazaki M., et al. (2011). In vitro and in vivo antifungal activities of E1210, a novel GPI-biosynthesis inhibitor. Antimicrobial Agents and Chemotherapy.

Other names

GPI-linked proteinsGlypiated proteinsGPI-anchored receptorsGPI-anchored enzymes

Complement C5 inhibition; Complement C3 inhibition; Gwt1 protein inhibition