Figure 12–52 The attachment of a GPI anchor to a protein in the ER. Gpianchored proteins are targeted to the er membrane by an n-terminal signal sequence (not shown), which is removed (see figure 12–42). immediately after the completion of protein synthesis, the precursor protein remains anchored in the er membrane by a hydrophobic C-terminal sequence of 15–20 amino acids; the rest of the protein is in the er lumen. Within less than a minute, an enzyme in the er cuts the protein free from its membrane-bound C-terminus and simultaneously attaches the new C-terminus to an amino group on a preassembled Gpi intermediate. The sugar chain contains an inositol attached to the lipid from which the Gpi anchor derives its name. it is followed by a glucosamine and three mannoses. The terminal mannose links to a phosphoethanolamine that provides the amino group to attach the protein. The signal that specifies this modification is contained within the hydrophobic C-terminal sequence and a few amino acids adjacent to it on the lumenal side of the er membrane; if this signal is added to other proteins, they too become modified in this way. Because of the covalently linked lipid anchor, the protein remains membrane-bound, with all of its amino acids exposed initially on the lumenal side of the er and eventually on the exterior of the plasma membrane.
lipid bilayer of ER phosphatidic they can in principle be released from cells in soluble form in response to signals Figure 12–53 The synthesis of phosphatidylcholine. as illustrated, this that activate a specific phospholipase in the plasma membrane. Trypanosome phospholipid is synthesized from glycerol parasites, for example, use this mechanism to shed their coat of GPI-anchored 3-phosphate, cytidine-diphosphocholine surface proteins when attacked by the immune system. GPI anchors may also be (CDp-choline), and fatty acids delivered used to direct plasma membrane proteins into lipid rafts and thus segregate the to the er by a cytosolic fatty acid binding proteins from other membrane proteins (see Figure 10–13).
protein.
The er assembles most lipid Bilayers
The ER membrane is the site of synthesis of nearly all of the cell’s major classes of lipids, including both phospholipids and cholesterol, required for the production of new cell membranes. The major phospholipid made is phosphatidylcholine, which can be formed in three steps from choline, two fatty acids, and glycerol phosphate (Figure 12–53). Each step is catalyzed by enzymes in the ER membrane, which have their active sites facing the cytosol, where all of the required metabolites are found. Thus, phospholipid synthesis occurs exclusively in the cytosolic leaflet of the ER membrane. Because fatty acids are not soluble in water, they are shepherded from their sites of synthesis to the ER by a fatty acid binding protein in the cytosol. After arrival in the ER membrane and activation with CoA, acyl transferases successively add two fatty acids to glycerol phosphate to produce phosphatidic acid. Phosphatidic acid is sufficiently water-insoluble to remain in the lipid bilayer; it cannot be extracted from the bilayer by the fatty acid binding proteins. It is therefore this first step that enlarges the ER lipid bilayer. The later steps determine the head group of a newly formed lipid molecule and therefore the chemical nature of the bilayer, but they do not result in net membrane growth. The two other major membrane phospholipids—phosphatidylethanolamine and phosphatidylserine (see Figure 10–3)—as well as the minor phospholipid phosphatidylinositol (PI), are all synthesized in this way.