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WIREs Membr Transp Signal

The challenge of determining the role of Rh glycoproteins in transport of NH3 and NH4 +

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The mammalian Rh glycoproteins belong to the solute transporter family SLC42 and include the erythroid Rh‐associated glycoprotein (RhAG) and two epithelial membrane molecules Rhbg (human RhBG) and Rhcg (RhCG). Mammalian Rh glycoproteins are closely related to the ammonium transporters of the yeast (MEP proteins) and bacteria (Amt). Rhbg and Rhcg are expressed in several mammalian tissues including liver, kidney, skin, lung, and GI tract. In the kidney they are expressed in α‐intercalated cells and principal cells of the collecting duct. Whereas Rhbg is strictly present in the basolateral membrane; Rhcg is reported to be at both apical membrane and basolateral membranes. Recent functional studies strongly support a role of Rh glycoproteins in NH4+ transport. Other studies indicate that they mediate transport of CO2 and NH3. This review highlights the progress in determining the properties of Rh glycoproteins and the challenging questions that continue to hinder understanding their function and their physiological role. WIREs Membr Transp Signal 2014,3:53–61. doi: 10.1002/wmts.105

pHi and current changes caused by 5 mM NH4Cl (NH3/NH4+) in Rhbg and H2O‐injected oocytes. Exposing oocytes that express Rhbg to 5 mM NH4Cl caused a faster intracellular acidification (pHi tracing) and a bigger inward current than in H2O‐injected oocytes (Bar graph).
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CO2 transport in H2O‐injected and Rhbg‐expressing oocytes. Exposing oocytes to a solution containing 1.5% CO2 from a solution essentially CO2‐free caused a decrease in pHi presumably due to influx of CO2 and generation of intracellular H+. In oocytes expressing Rhbg, the CO2‐induced pHi decrease is substantially faster than in H2O‐injected oocytes.
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Summary of the effects of NH3/NH4+ and MA/MA+ on Rhbg, Rhcg, and H2O‐injected oocytes. The effects of NH3/NH4+ and MA/MA+ on pHi in oocytes expressing Rhcg are more pronounced than in H2O‐injected oocytes but significantly less than in oocytes expressing Rhbg.
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pHi changes induced by NH4+ and MA+ in oocytes expressing Rhbg. Exposing oocytes to NH4+ (5 mM) caused a decrease in pHi and depolarization of the cell (segment ab). Exposing oocytes to MA+ (5 mM) caused an increase in pHi but still caused a depolarization of the cell (segment cd).
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Ammonium (NH4+) and methyl ammonium (MA+)‐induced currents in oocytes expressing (a) Rhbg or (b) injected with H2O. NH4+ and MA+ caused inward currents in oocytes expressing Rhbg (upper tracing). In H2O‐injected oocytes (lower tracing) NH4+ induced a smaller current than in Rhbg oocytes whereas MA+ did not induce any current.
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