SEARCH

SEARCH BY CITATION

Keywords:

  • band 3;
  • gas exchange;
  • glycophorin A;
  • glycophorin B;
  • Miltenberger blood group antigen subtype III;
  • RhAG

In Taiwan, Miltenberger blood group antigen subtype III (Mi.III) is the second most important blood group antigen following ABO. Mi.III presumably evolved from homologous recombination between GYPA and GYPB, and expresses a hybrid configuration of glycophorin B-A-B and the Mur antigen in the crossover region.

GPA and GPB oligomerize on the erythrocyte cell membrane. GPA also forms protein complexes with band 3 and facilitates band 3 expression. GPB is believed not to involve in the GPA-band 3 interaction. In Mi.III+ blood, half or all GPB is replaced with the glycophorin BAB hybrid, Gp.Mur. We previously showed that upon heterologous expression in HEK-293 cells, Gp.Mur, like GPA, facilitates the protein expression of band 3. Quantitative proteomics by iTRAQ revealed 25–67% more band 3 on the Mi.III+ erythrocyte membrane, as compared to the non-Mi.III. Band 3 is a Cl/HCO3 exchanger. With more band 3 protein expression, Mi.III+ RBCs exhibit larger capacities for Cl/HCO3 exchange across the cell membrane. Conceivably, those with the Mi.III phenotype might have larger capacities for CO2 respiration.

On the other hand, GPB is a component of the Rh protein complex, and has been shown to assist the surface expression of RhAG. Because GPB is half or completely replaced by Gp.Mur in Mi.III+ RBCs, we also examined if the expression of the Rh complexes could be affected in Mi.III. We found that homologous Mi.III RBCs exhibit reduced levels of RhAG and Rh antigens. The functions of Rh polypeptides and RhAG in erythrocytes are unclear, but RhAG in other species might function as gas channels for physiologically important molecules such as CO2, NH3, NO, and/or O2. Thus, substitution of GPB with Gp.Mur in Mi.III+ RBCs affects the structure of the band 3/Rh-associated macrocomplex, and is expected to affect functional coordination within the metabolon of O2/CO2 gas exchange as well.