Biological Functions and Biosynthesis of Glycolipid-Anchored Membrane Proteins

Abstract

The glycosylinositol phospholipid (GPI) anchors of proteins such as Thy-1 of neurons and lymphocytes and the variant surface glycoprotein of African trypanosomes are posttranslationally linked to the C-terminus of the corresponding proteins (Figure 1) (Cross, 1990; Ferguson et al., 1988; Low and Saltiel, 1988; Tartakoff et al., 1990). The in vivo sensitivity of many anchor units to microbial phosphatidylinositol (PI)-specific phospholipases implies that they do not traverse the lipid bilayer. Such proteins cannot be subject to many cytoplasmic events, such as direct linkage to the cytoskeleton and phosphorylation, which impact on transmembrane proteins (Figure 2). It was therefore anticipated both that the lateral diffusion of GPI-anchored proteins would be high and that these proteins might be released by physiologically important phospholipases. The evidence in support of such conjectures with regard to function is, however, difficult to generalize. For example, GPI-anchored class I histocompatibility antigens do appear to gain access to much of the cell surface (Edidin and Stroynowski, 1991), although their lateral diffusion is not uniformly higher than for transmembrane proteins (Bulow et al., 1988; Phelps et al., 1988). Furthermore, although there are a few experimental reports describing release of GPI-anchored proteins (Chan et al., 1988; He et al., 1987; Huizinga et al., 1988) and although soluble forms of several GPI-anchored proteins are found in extracellular fluids (Almqvist and Carlsson, 1988; Epstein et al., 1986; Overath et al., 1983; Quentmeier et al., 1987), release appears to be the exception rather than the rule.