AUTHOR=Hsu Kate 

TITLE=Exploring the Potential Roles of Band 3 and Aquaporin-1 in Blood CO2 Transport–Inspired by Comparative Studies of Glycophorin B-A-B Hybrid Protein GP.Mur

JOURNAL=Frontiers in Physiology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2018.00733

DOI=10.3389/fphys.2018.00733

ISSN=1664-042X

ABSTRACT=<p>The Cl<sup>—</sup>/HCO<sub>3</sub><sup>—</sup> exchanger band 3 is functionally relevant to blood CO<sub>2</sub> transport. Band 3 is the most abundant membrane protein in human red blood cells (RBCs). Our understanding of its physiological functions mainly came from clinical cases associated with band 3 mutations. Severe reduction in band 3 expression affects blood HCO<sub>3</sub><sup>—</sup>/CO<sub>2</sub> metabolism. What could happen physiologically if band 3 expression is elevated instead? In some areas of Southeast Asia, about 1–10% of the populations express GP.Mur, a glycophorin B-A-B hybrid membrane protein important in the field of transfusion medicine. GP.Mur functions to promote band 3 expression, and GP.Mur red cells can be deemed as a naturally occurred model for higher band 3 expression. This review first compares the functional consequences of band 3 at different levels, and suggests a critical role of band 3 in postnatal CO<sub>2</sub> respiration. The second part of the review explores the transport of water, which is the other substrate for intra-erythrocytic CO<sub>2</sub>/HCO<sub>3</sub><sup>—</sup> conversion (an essential step in blood CO<sub>2</sub> transport). Despite that water is considered unlimited physiologically, it is unclear whether water channel aquaporin-1 (AQP1) abundantly expressed in RBCs is functionally involved in CO<sub>2</sub> transport. Research in this area is complicated by the fact that the H<sub>2</sub>O/CO<sub>2</sub>-transporting function of AQP1 is replaceable by other erythrocyte channels/transporters (e.g., UT-B/GLUT1 for H<sub>2</sub>O; RhAG for CO<sub>2</sub>). Recently, using carbonic anhydrase II (CAII)-filled erythrocyte vesicles, AQP1 has been demonstrated to transport water for the CAII-mediated reaction, CO<sub>2(g)</sub> + H<sub>2</sub>O ⇌ HCO<sub>3</sub><sup>—</sup><sub>(aq)</sub> + H<sup>+</sup><sub>(aq)</sub>. AQP1 is structurally associated with some population of band 3 complexes on the erythrocyte membrane in an osmotically responsive fashion. The current findings reveal transient interaction among components within the band 3-central, CO<sub>2</sub>-transport metabolon (AQP1, band 3, CAII and deoxygenated hemoglobin). Their dynamic interaction is envisioned to facilitate blood CO<sub>2</sub> respiration, in the presence of constantly changing osmotic and hemodynamic stresses during circulation.</p>