The special blood group antigen Mi.III exhibits a characteristic hybrid structure of glycophorin A (GPA) and glycophorin B, termed Gp.Mur. This phenotype has exceptionally high occurrence rates in several indigenous tribes in Taiwan ( approximately 21.2%-88.4%). Because glycophorin/Miltenberger begins interaction with anion exchanger-1 (AE1) in the endoplasmic reticulum, we hypothesized that the AE1-based macrocomplexes on erythrocyte membranes obtained from Mi.III(+) people could be differentiated from those obtained from non-Miltenberger people. Quantitative mass spectrometric comparison of the AE1-based complexes by iTRAQ (Applied Biosystems) revealed 25% to 67% higher expression of AE1 in Mi.III(+) erythrocytes. In accordance with the higher AE1 level, the Mi.III(+) erythrocytes exhibited superior HCO(3)(-) capacities, pH homeostasis, and osmotic resistance. Cotransfection experiments in HEK293 cells showed that Gp.Mur, like GPA, enhanced trafficking of AE1 to the plasma membrane. In summary, the increased surface expression of AE1 in Mi.III(+) erythrocytes could be attributed to the additive effect of GPA and Gp.Mur coexpression.
