Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene.
Glycosylphosphatidylinositol (GPI) serves as a membrane anchor for a large number of eukaryotic proteins. A genetic approach was used to investigate the biosynthesis of GPI anchor precursors in mammalian cells. T cell hybridoma mutants that cannot synthesize dolichol-phosphate-mannose (Dol-P-Man) also do not express on their surface GPI-anchored proteins such as Thy-1 and Ly-6A. These mutants cannot form mannose-containing GPI precursors. Transfection with the yeast Dol-P-Man synthase gene rescues the synthesis of both Dol-P-Man and mannose-containing GPI precursors, as well as the surface expression of Thy-1 and Ly-6A, suggesting that Dol-P-Man is the donor of at least one mannose residue in the GPI core.
DeGasperi
R
R
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Massachusetts General Hospital, Boston 02114.
Thomas
L J
LJ
Sugiyama
E
E
Chang
H M
HM
Beck
P J
PJ
Orlean
P
P
Albright
C
C
Waneck
G
G
Sambrook
J F
JF
Warren
C D
CD
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D002462:Cell Membrane / Q000502:physiology; D004287:Dolichol Monophosphate Mannose / Q000378:metabolism; D005800:Genes, Fungal; D006017:Glycolipids / Q000096:biosynthesis*; D017261:Glycosylphosphatidylinositols; D006825:Hybridomas; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000235:genetics; D018800:Thy-1 Antigens; D014162:Transfection
D000950:Antigens, Ly; D000954:Antigens, Surface; D006017:Glycolipids; D017261:Glycosylphosphatidylinositols; D010716:Phosphatidylinositols; D018800:Thy-1 Antigens; D004287:Dolichol Monophosphate Mannose