Lipids glycosylphosphatidylinositol-anchored

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. 

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

Serrano AA, Schenkman S, Yoshida N et al. The lipid saucture of the glycosylphosphatidylinositol-anchored mucin-like sialic acid acceptors of Trypanosoma cruzi changes during parasite differentiation from epimastigotes to infective metacyclic trypomastigote forms. J Biol Chem 1995 270 27244-27253. 

The four major types of protein lipidation are A-myristoylation, palmitoylation, prenylation and glycosylphosphatidylinositol-anchor (GPI-anchor) addition (Table 1). 

Heise, N., de Almeida, M. L. and Ferguson, M. A. (1995) Characterization of the lipid moiety of the glycosylphosphatidylinositol anchor of Trypanosoma cruzi lG7-antigen. Mol Biochem. Parasit., 70, 71-84. 

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... 

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. 

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. 

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