TCB Publications - Abstract

Marie Michenkova, Sara Taki, Matthew C. Blosser, Hyea J. Hwang, Thomas Kowatz, Fraser J. Moss, Rossana Occhipinti, Xue Qin, Soumyo Sen, Eric Shinn, Dengke Wang, Brian S. Zeise, Pan Zhao, Noah Malmstadt, Ardeschir Vahedi-Faridi, Emad Tajkhorshid, and Walter F. Boron. Carbon dioxide transport across membranes. Interface Focus, 11:20200090, 2021.

MICH2021-ET Carbon dioxide (CO2) movement across cellular membranes is passive and, at a nanoscopic scale, governed by Fick’s law of diffusion. Until recently, we believed that gases cross biological membranes exclusively by dissolving in and then diffusing through membrane lipid. However, the observation that some membranes are CO2 impermeable led to the discovery of a gas molecule’s moving through a channel, namely, CO2 diffusion through aquaporin-1 (AQP1). Later work demonstrated CO2 diffusion through rhesus (Rh) proteins and NH3 diffusion through both AQPs and Rh proteins. The tetrameric AQPs exhibit differential selectivity for CO2 versus NH3 versus H2O, reflecting physico-chemical differences among the small molecules, as well as among the hydrophilic monomeric pores and hydrophobic central pores of various AQPs. Preliminary work suggests that NH3 moves through the mono- meric pores of AQP1, whereas CO2 moves through both monomeric and central pores. Initial work on AQP5 indicates that it is possible to create a metal-binding site on the central pore’s extracellular face, thereby block CO2 movement. The trimeric Rh proteins have monomers with hydrophilic pores surrounding a hydrophobic central pore. Preliminary work on the bacterial Rh homologue AmtB suggests that gas can diffuse through the central pore and three sets of interfacial clefts between monomers. Finally, initial work indi- cates that CO2 diffuses through the electrogenic Na/HCO3 cotransporter NBCe1. At least in some cells, CO2-permeable proteins could provide impor- tant pathways for transmembrane CO2 movements. Such pathways could be amenable to cellular regulation and could become valuable drug targets.

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