Structural and functional roles of glycosylphosphoinositides.

Many proteins are anchored to the cell surface by hydrophobic interactions with the membrane bilayer. Several structural motifs are utilized for membrane anchorage in mammalian cells, including the covalent attachment of proteins to lipids (Saltiel et al., 1991). One such mechanism involves the linkage of proteins to a glycosylated form of phosphatidylinositol (PI), termed glycosylphosphatidylinositol (GPI). This mechanism has been detected in a variety of cell types and is utilized by over 100 membrane proteins (Ferguson and Williams, 1988; Low and Saltiel, 1988). Additionally, a glycophospholipid with several structural similarities to the GPI anchor has been described in a number of cell types (Saltiel and Cuatrecasas, 1986, 1988; Saltiel et al., 1986). This lipid, which shares the core structure of the membrane anchor and may represent a biosynthetic intermediate, undergoes a phospholipase C (PLC)-catalyzed hydrolysis in response to insulin and functionally related growth factors, generating an aqueous glycan in cells that mediates some of the actions of the hormone (Saltiel and Cuatrecasas, 1986; Saltiel et al., 1986). Although the precise relationship between the protein anchored and the hormone-sensitive free form of the lipid remains unknown, numerous similarities suggest that these glycolipids may participate in related functions in cellular regulation. This chapter focuses on the unusual properties and important roles of this unique class of lipids in cellular regulation.