Signal Transduction Via GPI-Anchored Membrane Proteins

Abstract

Eukaryotic cells carry upon their cell surfaces a number of proteins which are anchored in the membrane via glycosylphosphatidylinositol (GPI) membrane anchors¹ These proteins are attached to the cell membrane by hydrophobic attraction of the phospholipid tails of the GPI-anchor with lipids in the outer face of the plasma membrane bilayer. Consequently, they neither span the cell membrane nor do they interact directly with intracellular components. During intracellular transport, GPI anchors recruit specialized lipids and glycolipids^(2,3,4). Acquisition of these lipids renders GPI-anchored proteins insoluble in a number of non-ionic detergents, and enables their enrichment in cell lysates by density-gradient centrifugation. These associated lipids, which include sphingomyelin and cholesterol, may alter the cell-surface distribution of GPI-linked molecules relative to their non-GPI-linked counterparts, and this is currently the subject of intensive study⁽⁵⁾. These GPI-rich detergent-insoluble complexes also contain a number of other proteins which are not GPI-linked, and it is thought that these other molecules may play a key role in the functional properties of GPI anchors. It was shown using photobleaching recovery (FRAP) or single particle tracking (SPT) techniques⁽⁶⁾ that GPI-linked molecules are not freely mobile in the cell membrane, an expected finding for a molecule which is associated only with the outer lipid leaflet of the plasma membrane. This finding implies that the mobility of Thy-1 is influenced by its association with immobile components of the membrane, and thus, indirectly, with the cytoskeleton. These observations implicate transmembrane molecules in the interactions of GPI-linked molecules with cytoplasmic and cytoskeletal components.