Glycosylphosphatidylinositol, lipid anchor

Much of the plasma membrane cholesterol is removed by incubating cells with P-methylcyclodextrin for several hours. Cells remain viable after this treatment but the raft fraction is reduced and it is inferred that the depleted proteins are normally associated with cholesterol-dependent lipid rafts. Some, but not all, glycosylphosphatidylinositol (GPI)-anchored proteins are recovered in the fractions defined by this procedure. 

Furthermore, according to Howell and Crine (1996), type IV represents multimers of subunits, type V represents proteins that are anchored to the membrane by a covalently linked lipid moiety only, and type VI represents those anchored both by a transmembrane domain and the glycosylphosphatidylinositol (GPI) anchor (see Section III,C,3). 

Molecular targets have been elucidated for Dm-AMPl and Rs-AFP2. Dm-AMPl was found to bind plasma membranes from Neurospora crassa and Saccharomyces cerevisiae in a saturable manner and it competed with closely related defensins for binding. Mutational studies with S. cerevisiae identified lipid raffs containing sphingolipids as a molecular target " while glycosylphosphatidylinositol (GPI)-anchored proteins could be... 

Receptors anchored to the plasma membrane by lipids Glycosylphosphatidylinositol (GPI)-anchored proteins and glycolipids... 

G. Sipos, F. Reggiori, C. Vionnet, and A. Conzelmann, Alternative lipid remodelling pathways for glycosylphosphatidylinositol membrane anchors in Saccharomyces cerevisiae, EMBO. /., 16 (1997) 3494—3505. 

R. Schroeder, E. London, and D. Brown, Interactions between saturated acyl chains confer detergent resistance on lipids and glycosylphosphatidylinositol (GPI)-anchored proteins GPI-an-chored proteins in liposomes and cells show similar behavior, Proc. Natl. Acad. Sci. USA, 1994, 91, 12130-12134. 

Glycosylphosphatidylinositol (GPI) anchors are found in many cell surface proteins in eukaryotes, which tether them to the extracellular side of the plasma membrane. The GPI anchor is attached to the C-terminus of a protein via a phosphoetha-nolamine linkage. GPIs and GPI-anchored proteins are built up in the ER and then the modified proteins transit to the cell surface. This posttranslational glyco-lipid modification is mediated by the GPI transamidase (GPI-T) in the ER lumen. The GPI anchor can be hydrolysed by phosphatidylinositol-specific phospholipase C or D (PLC or PLD) which releases the protein moiety into the extracellular milieu... 

M. C. Field, A. K. Menon G. A. Cross. A glycosylphosphatidylinositol protein anchor from procyclic stage Trypanosoma brucei lipid structure and biosynthesis. EMBO J, 1991,10, m -111,9. 

To better understand the structural properties of the lipoproteins involved in intracellular signaling pathways, synthetic lipopeptides are required as model compounds. In this context, to bypass the enzyme-catalyzed lipidation occurring in nature, optimized synthetic procedures have been elaborated for the more simple lipo-derivatives (for comprehensive reviews see ref[1]). However, similar efficient synthetic procedures for the glycosylphosphatidylinositol anchor are still lacked. 

Phosphatidylinositol (PI), a major component of membrane lipids, is formed by displacement of CMP from CMD-dialylglycerol by n/i/o-inositol.186 It is also converted into a variety of less abundant phosphory-lated derivatives that engage in signaling activities (see Fig. 11-9). In addition, PI is a component of the glycosylphosphatidylinositol (GPI) membrane anchors for suface proteins (Fig. 8-13). Free GPI anchors, lacking bound proteins, are also present in membranes. 

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