Cell-Surface Anchoring of Proteins via Glycosyl-Phosphatidylinositol Structures

Abstract

A class of membrane molecules has been identified whose primary translation product includes a COOH-terminal protein sequence that signals attachment of a glycosyl-phosphatidylinositol anchor at a COOH-terminal residue that is newly formed by cleavage of the signaling sequence. This class includes a wide diversity of protein types from eukaryotes at many stages of evolution. The structures of the glycosyl-phosphatidylinositol anchors are being resolved, but their functions aside from membrane attachment and dynamics remain to be determined.

Membrane Association of Lipoprotein Lipase and a cAMP-Binding Ectoprotein in Rat Adipocytes

“…The nonreducing end is linked to ethanolamine via a phosphodiester bridge. From this conserved core glycan various carbohydrate and/ or phosphoethanolamine residues may branch off [for a review see Ferguson and Williams (1988), Low (1989), and McConville and Ferguson (1993l. During the biosynthesis of GPI-proteins, the amino group of ethanolamine of the complete preformed GPI structure is coupled in a pseudo transpeptidation reaction to the carboxy terminus of the mature fully translated polypeptide chain, thereby replacing a transmembrane domain present in the protein precursor [for a review see Doering et al (1990) and Thomas et al (1990)l.…”

Identification of a Novel Neural Cell Adhesion Molecule-related Gene with a Potential Role in Selective Axonal Projection

“…1), and thus the cloned gene most likely encodes proteins recognized by the Rb-8 antibody. At the COOH terminus of the short form there is a run of hydrophobic amino acids and no cytoplasmic domain, which is compatible with attachment to the cell membrane by a phosphatidylinositol anchor (18). The long form contained a 25-amino acid potential transmembrane region and a 106-amino acid intracellular domain.…”

Mammalian PIG-L and its yeast homologue Gpi12p are N-acetylglucosaminylphosphatidylinositol de-N-acetylases essential in glycosylphosphatidylinositol biosynthesis

“…Glycosylphosphatidylinositol (GPI) is used to anchor various eukaryotic proteins to the cell-surface membrane [1,2]. GPIanchored proteins are found in yeast [3], mammals [2] and plants [4] but are especially abundant in protozoan parasites [5].…”

“…The common core structure of GPI consists of inositol phospholipid, GlcN, three mannoses and an ethanolamine phosphate [1]. The biosynthesis of GPI occurs on the membrane of the endoplasmic reticulum (ER) [7].…”

“…Later, three mannoses from dolichol-phosphate-mannose and an ethanolamine phosphate from phosphatidylethanolamine are added sequentially [7]. The core is variously modified with side groups during or after its synthesis [1]. Finally, an amino group of the terminal ethanolamine of the assembled GPI is linked to the C-terminus of a precursor protein [8].…”