Abstract
At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs). The protein moiety of GPI-APs lacking transmembrane domains is anchored to the plasma membrane with GPI covalently attached to the C-terminus. The GPI consists of the conserved core glycan, phosphatidylinositol and glycan side chains. The entire GPI-AP is anchored to the outer leaflet of the lipid bilayer by insertion of fatty chains of phosphatidylinositol. Because of GPI-dependent membrane anchoring, GPI-APs have some unique characteristics. The most prominent feature of GPI-APs is their association with membrane microdomains or membrane rafts. In the polarized cells such as epithelial cells, many GPI-APs are exclusively expressed in the apical surfaces, whereas some GPI-APs are preferentially expressed in the basolateral surfaces. Several GPI-APs act as transcytotic transporters carrying their ligands from one compartment to another. Some GPI-APs are shed from the membrane after cleavage within the GPI by a GPI-specific phospholipase or a glycosidase. In this review, I will summarize the current understanding of GPI-AP biosynthesis in mammalian cells and discuss examples of GPI-dependent functions of mammalian GPI-APs.
Highlights
At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs) [1]
The pathway is initiated on the cytoplasmic side of the endoplasmic reticulum (ER) by GPI N-acetylglucosaminyl transferase (GPI-GnT), which catalyses the transfer of N-acetylglucosamine (GlcNAc) from uridine diphosphate (UDP)-GlcNAc to the 6-position of inositol to generate GlcNAc-PI
When the precursor proteins of GPI-APs are not processed by GPI transamidase for GPI attachment, they are retrotranslocated for degradation by ubiquitin- and proteasomedependent ER-associated degradation (ERAD) [113]
Summary
At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs) [1]. GPI-APs are integral membrane proteins present on the cell surface. The protein moiety of GPI-APs is basically hydrophilic lacking transmembrane domains, and is anchored to the plasma membrane (PM) with GPI moiety covalently attached to the C-terminus (figure 1). The entire GPI-AP is anchored to the outer leaflet of the lipid bilayer by insertion of hydrocarbon chains of PI (figure 1). For lipid–lipid interactions, saturated lipid chains of both sphingolipids and GPI anchors are critical [8,9]. For the regulation by cortical actin, transbilayer interaction between lipid moiety of GPI-APs in the outer leaflet and phosphatidylserine in the inner leaflet is critical [13]. Src family tyrosine kinases [14] and other proteins such as phospholipase Cγ (PLCγ) are associated with membrane microdomains in the inner leaflet. Biogenesis of GPI-APs: post-translational modification of proteins with the GPI mediated by GPI transamidase
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