Miltenberger blood group antigen type III (Mi.III) enhances the expression of band 3

Abstract

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 (ϳ21.2%-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

Miltenberger phenotypes are glycophorin variants: a review

“…Presence of GP.Mur may provide resistance to Plasmodium falciparum [30]. The presence of GP.Mur in the RBC membrane can up-regulate the amount of band 3 on the RBC surface thereby making the RBC more resistant to osmotic stress [31]. GP.Hop, which expresses TSEN but not Hil, is identical to GP.Bun except that the allele responsible for GP.Hop encodes S, whereas the allele for GP.Bun encodes the s antigen.…”

Physiological Implications of Miltenberger blood group antigen subtype III (Mi.III)

“…As Mi.III expression affects the interface between RhAG and GPB ⁄ Gp.Mur and the interface between band 3 and GPA ⁄ Gp.Mur, conceivably band 3 and the Rh complex are structurally linked by oligomerization of GPA and GPB ⁄ Gp.Mur. The protein-protein interaction between GPA and its homologous counterparts -GPB ⁄ Gp.Mur is substantial and stable, since GPA-GPB ⁄ Gp.Mur heterodimers could be readily observed on SDS-PAGE, with similarly strong band intensities as that for GPA homodimers or GPB homodimers [16]. We also recently found that GPA and GPB ⁄ Gp.Mur partially colocalize in transfected mammalian cultured cells (unpublished data).…”

“…Since Gp.Mur is a hybrid protein of GPB and GPA, it might bear similar or modified chaperone activities. We previously compared the chaperone activities of GPA versus Gp.Mur for band 3 in heterologous expression experiments, and found that Gp.Mur is as potent as GPA in enhancing the protein production and surface expression of band 3 [16]. On the other hand, GPB has relatively small effects on the surface expression of band 3.…”

“…The impacts of Gp.Mur on erythrocyte band 3 activities [16]. The greater pH i -buffering capacity of Mi.III is expected to be an asset for one's health or even survival under certain pathophysiological stress that disturbs pH homoeostasis.…”

“…It is thus conceivable that expression of Gp.Mur instead of GPB in Mi.III erythrocytes shall enhance the overall expression of band 3. Indeed, from an iTRAQ proteomic experiment that quantitatively compared protein components of the band 3-associated macrocomplexes in Mi.III versus non-Mi.III erythrocytes, there is 25% or more band 3 on the surface of Mi.III erythrocytes [16]. Band 3 and Rh complex proteins are structurally linked.…”