Recent progress in synthetic and biological studies of GPI anchors and GPI-anchored proteins

Abstract

Summary Covalent attachment of glycosylphosphatidylinositols (GPIs) to the protein C-terminus is one of the most common posttranslational modifications in eukaryotic cells. In addition to anchoring surface proteins to the cell membrane, GPIs also have many other important biological functions, determined by their unique structure and property. This account has reviewed the recent progress made in disclosing GPI and GPI-anchored protein biosynthesis, in the chemical and chemoenzymatic synthesis of GPIs and GPI-anchored proteins, and in understanding the conformation, organization, and distribution of GPIs in the lipid membrane.

Structural determinants of protein partitioning into ordered membrane domains and lipid rafts

“…GPI anchors are constituted of a phosphatidylinositol, coupled via a glucosamine, three mannose residues and a phosphoethanolamine group to the C-terminus of the protein via amide bond. While the two acyl chains of the lipid anchor can be unsaturated or saturated, they are most often saturated (Yu, Guo et al 2013). GPI-anchored proteins (GPIAPs) were some of the first to be identified in DRMs, with detergent resistance acquired only after trafficking through the trans-Golgi network, suggesting that it was not protein-intrinsic, but rather a function of membrane environment (Brown and Rose 1992).…”

Tissue Non-specific Alkaline Phosphatase (TNAP) in Vessels of the Brain

“…The addition of GPI on the TNAP occurs in the lumen of endoplasmic reticulum (ER) where the GPI biosynthesis takes place also [see details in (Yu et al 2013)]. This attachement process of GPI on protein involves an enzymatic complex named GPI transaminidase.…”

Glycosylphosphatidylinositol-anchored proteins as chaperones and co-receptors for FERONIA receptor kinase signaling in Arabidopsis

“…Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are cell surface-located proteins known to play important roles in regulating a broad range of biological processes including growth, morphogenesis, reproduction, and disease pathogenesis in eukaryotes ( Lingwood and Simons, 2010 ; Fujita and Kinoshita, 2012 ; Yu et al, 2013 ). They localize to sphingolipid- and cholesterol-enriched domains in the cell membrane where they are believed to play key roles in regulating cell surface signaling dynamics, although much remains to be learned about their precise functional mechanisms.…”