Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO₂ transport

Human CO₂ respiration requires rapid conversion between CO₂ and HCO₃^- Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO₃^- flux across the cell membrane. These 2 proteins are core components of the CO₂ transport metabolon. Intracellular H₂O is necessary for CO₂/HCO₃^- conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO₂ transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO₂/HCO₃^- exchange. By demonstrating AQP1 as a mobile component of the CO₂ transport metabolon, our results uncover a potential role of water channel in blood CO₂ transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO₂ transport.