The Role of Lipid Anchored Proteins in the Development of the Membrane Raft Hypothesis

Before reverting to the heart of the matter, it is useful to examine why glycosyl-phosphatidylinositol (GPI)-anchored proteins have been used as markers for rafts. GPI-APs are a class of extracytoplasmic proteins that undergo a post-translational lipid modification that results in the exchange of an often perfectly competent hydrophobic transmembrane protein anchor with a glycolipid, the GPI-anchor [7] (Fig. 3.3). The GPI-anchor is the sole anchor by which most of these proteins attach to membranes, and often is required for targeting to plasma membrane after their synthesis and post-translational lipid modification in the endoplasmic reticulum (ER) [8]. Diverse proteins are GPI-anchored, and thus the GPI-anchor has been implicated in providing functions such as specific sorting in the secretory and endocytic pathway [7,9], and signaling [6,10-12]. In addition, in most cells almost all of the GPI-anchored proteins are present in DRMs. The requirement for maintenance of specific lipid composition for these special sorting and signaling characteristics, and the fact that the GPI-anchor did not extend beyond the first leaflet of the bilayer, provided the impetus to examine the distribution of GPI-anchored proteins in cell membranes as indicators of lipid-based heterogeneity markers. Similar arguments are applicable to other lipid-tethered proteins where the lipid anchor appears to specific sorting and signaling specificity to the lipid-tethered proteins in question [13].

3.4 The Case For and Against DRMs as Evidence for "Rafts" in Cell Membranes | 49

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Essentials of Human Physiology

Essentials of Human Physiology

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