Mannosamine, a novel inhibitor of glycosylphosphatidylinositol incorporation into proteins.
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.
Lisanti
M P
MP
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021.
Field
M C
MC
Caras
I W
IW
Menon
A K
AK
Rodriguez-Boulan
E
E
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
D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D006595:Hexosamines; D010716:Phosphatidylinositols; D015800:Protozoan Proteins; C008322:mannosamine