title: Endocytosis of glycosylphosphatidylinositol-anchored proteins.
abstract: Glycosylphosphatidylinositol-anchored proteins (GPI-APs) represent an interesting amalgamation of the three basic kinds of cellular macromolecules viz. proteins, carbohydrates and lipids. An unusually hybrid moiety, the GPI-anchor is expressed in a diverse range of organisms from parasites to mammalian cells and serves to anchor a large number of functionally diverse proteins and has been the center of attention in scientific debate for some time now. Membrane organization of GPI-APs into laterally-organized cholesterol-sphingolipid ordered membrane domains or "rafts" and endocytosis of GPI-APs has been intensely debated. Inclusion into or exclusion from these membrane domains seems to be the critical factor in determining the endocytic mechanisms and intracellular destinations of GPI-APs. The intracellular signaling as well as endocytic trafficking of GPI-APs is critically dependent upon the cell surface organization of GPI-APs, and the associations with these lipid rafts play a vital role during these processes. The mechanism of endocytosis for GPI-APs may differ from other cellular endocytic pathways, such as those mediated by clathrin-coated pits (caveolae), and is necessary for unique biological functions. Numerous intracellular factors are involved in and regulate the endocytosis of GPI-APs, and these may be variably dependent on cell-type. The central focus of this article is to describe the significance of the endocytosis of GPI-APs on a multitude of biological processes, ranging from nutrient-uptake to more complex immune responses. Ultimately, a thorough elucidation of GPI-AP mediated signaling pathways and their regulatory elements will enhance our understanding of essential biological processes and benefit as components of disease intervention strategies.
authors.affiliation: Global Neuroscience Initiative Foundation, Los Angeles, CA, USA. slakhan@gnif.org
authors.forename: Shaheen E
authors.initials: SE
authors.lastname: Lakhan
authors.forename: Shefali
authors.initials: S
authors.lastname: Sabharanjak
authors.forename: Ananya
authors.initials: A
authors.lastname: De
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000737:chemistry; D004705:Endocytosis; D017261:Glycosylphosphatidylinositols / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry*; D008954:Models, Biological; D009154:Mutation; D011328:Prions / Q000378:metabolism; D011506:Proteins / Q000737:chemistry; D015398:Signal Transduction; D013107:Sphingolipids / Q000737:chemistry
chemical_list: D002966:Clathrin; D017261:Glycosylphosphatidylinositols; D008055:Lipids; D011328:Prions; D011506:Proteins; D013107:Sphingolipids