Glycosylphosphatidylinositol-anchored proteins (GPI-APs)

Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are a diverse class of cell surface molecules tethered to the plasma membrane by a glycolipid anchor. In the prostate, this group includes various receptors and enzymes, such as prostate stem cell antigen (PSCA), which are frequently overexpressed in malignant or hyperplastic tissues (Denmeade et al., 2012). These molecules serve as the primary docking sites for certain pore-forming toxins, most notably aerolysin and its derivatives, which bind to the GPI-anchor moiety or the associated protein complex (Fivaz et al., 2002). In therapeutic applications for localized prostate cancer and benign prostatic hyperplasia (BPH), engineered toxins like topsalysin (PRX302) are designed to target these GPI-anchored receptors. Topsalysin remains inactive until it is cleaved by prostate-specific antigen (PSA) in the local microenvironment; once activated, it binds to the GPI-anchored proteins to form transmembrane pores, leading to selective osmotic lysis and cell death (Sophiris Bio, 2024). This targeting strategy leverages the ubiquitous presence of GPI-anchored proteins on prostate cell membranes while maintaining specificity through localized enzymatic activation.

Other names

GPI-anchored receptorsGPI-linked proteinsGPI-anchored cell surface proteinsGPI-anchored receptors on prostate cell membranes

Binding to the GPI-anchor moiety or associated protein complex to initiate pore formation and cell lysis following enzymatic activation.