The structure, biosynthesis and functions of glycosylphosphatidylinositol anchors, and the contributions of trypanosome research.
The discovery of glycosylphosphatidylinositol (GPI) membrane anchors has had a significant impact on several areas of eukaryote cell biology. Studies of the African trypanosome, which expresses a dense surface coat of GPI-anchored variant surface glycoprotein, have played important roles in establishing the general structure of GPI membrane anchors and in delineating the pathway of GPI biosynthesis. The major cell-surface molecules of related parasites are also rich in GPI-anchored glycoproteins and/or GPI-related glycophospholipids, and differences in substrate specificity between enzymes of trypanosomal and mammalian GPI biosynthesis may have potential for the development of anti-parasite therapies. Apart from providing stable membrane anchorage, GPI anchors have been implicated in the sequestration of GPI-anchored proteins into specialised membrane microdomains, known as lipid rafts, and in signal transduction events.
Ferguson
M A
MA
Division of Molecular Parasitology and Biological Chemistry, Department of Biochemistry, The Wellcome Trust Building, University of Dundee, Dundee DD1 5EH, UK. majferguson@bad.dundee.ac.uk
D000818:Animals; D019281:Dimerization; D019143:Evolution, Molecular; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007891:Leishmania / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology; D008322:Mammals / Q000469:parasitology; D008358:Mannose / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D008958:Models, Molecular; D011499:Protein Processing, Post-Translational; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology*; D014349:Trypanosoma cruzi / Q000201:enzymology / Q000472:pathogenicity / Q000502:physiology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014774:Virulence
D017261:Glycosylphosphatidylinositols; D008563:Membrane Lipids; D008565:Membrane Proteins; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; D008358:Mannose