GPIanchored

GPIanchored refers to proteins that are tethered to the exterior of the cell membrane by a glycosylphosphatidylinositol (GPI) anchor rather than by a transmembrane domain. The GPI moiety is a glycolipid that inserts into the outer leaflet of the plasma membrane and is covalently attached to the C-terminus of the protein through a glycan core and an ethanolamine phosphate linkage. This attachment occurs in the endoplasmic reticulum via a GPI transamidase complex, which links the preassembled GPI to the ω-site of the protein after removal of a C-terminal signal sequence.

GPI-anchored proteins are often enriched in lipid rafts and participate in a wide range of cellular functions, including signal transduction, cell adhesion, receptor activity, enzymatic processes, and immune recognition. Examples include CD55 (decay-accelerating factor), CD59 (protectin), Thy-1 (CD90), and the prion protein PrP. Other examples include urokinase receptor (uPAR) and various parasite surface proteins. The GPI anchor can be remodeled within the secretory pathway, influencing membrane localization and protein shedding.

Release and regulation: GPI-anchored proteins can be cleaved from the membrane by enzymes such as phosphatidylinositol-specific phospholipases, generating soluble protein forms while preserving functional domains.

Clinical relevance: defects in GPI anchor biosynthesis or attachment lead to inherited GPI deficiency disorders, presenting with developmental delay, seizures, hypotonia, and multi-organ involvement. Studying GPI-anchored proteins aids understanding of cell surface organization, signaling, and host-pathogen interactions.