title: Mannosamine, a novel inhibitor of glycosylphosphatidylinositol incorporation into proteins.
abstract: Mannosamine (2-amino-2-deoxy D-mannose) is shown here to block the incorporation of glycosylphosphatidylinositol (GPI) into GPI-anchored proteins. The amino sugar drastically reduced the surface expression of a recombinant GPI-anchored protein in polarized MDCK cells, converted this apical membrane-bound protein to an unpolarized secretory product and blocked the expression of endogenous GPI-anchored proteins. Furthermore, it specifically inhibited the incorporation of [3H]ethanolamine (a GPI component) into mammalian and trypanosomal GPI-anchored proteins and into a well characterized GPI-lipid of Trypanosoma brucei. These results suggest that mannosamine converted an apical GPI-anchored protein to a non-polarized secretory product by depleting transfer competent GPI-precursor lipids. Our inhibitor studies provide new independent evidence for the apical targeting role of GPI in polarized epithelia and open the way towards a greater understanding of the functional role of GPI in membrane trafficking and cell regulation.
authors.affiliation: Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021.
authors.forename: M P
authors.initials: MP
authors.lastname: Lisanti
authors.forename: M C
authors.initials: MC
authors.lastname: Field
authors.forename: I W
authors.initials: IW
authors.lastname: Caras
authors.forename: A K
authors.initials: AK
authors.lastname: Menon
authors.forename: E
authors.initials: E
authors.lastname: Rodriguez-Boulan
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D006017:Glycolipids / Q000096:biosynthesis / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols; D006595:Hexosamines / Q000378:metabolism*; D009154:Mutation; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism*; D011233:Precipitin Tests; D015800:Protozoan Proteins / Q000378:metabolism*; D014346:Trypanosoma brucei brucei / Q000378:metabolism
chemical_list: D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D006595:Hexosamines; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; C008322:mannosamine