Molecular physiology of the Rh ammonia transport proteins

Abstract

Recent studies have identified a new family of ammonia-specific transporters, Rh glycoproteins, which enable NH3-specific transport. The purpose of this review is to summarize recent evidence regarding the role of Rh glycoproteins in renal ammonia transport. The Rh glycoproteins, RhAG/Rhag, RhBG/Rhbg and RhCG/Rhcg, transport ammonia in the form of molecular NH3, although there is some evidence suggesting the possibility of NH4 transport. RhAG/Rhag is expressed only in erythrocytes, and not in the kidney. Rhbg and Rhcg are expressed in distal nephron sites, from the distal convoluted tubule through the inner medullary collecting duct, with basolateral Rhbg expression and both apical and basolateral Rhcg expression. Whether Rhbg contributes to renal ammonia transport remains controversial. Rhcg expression parallels ammonia excretion in multiple experimental models and genetic deletion studies, both global and collecting duct-specific, demonstrate a critical role for Rhcg in both basal and acidosis-stimulated renal ammonia excretion. X-ray crystallography has defined critical structural elements in Rh glycoprotein-mediated ammonia transport. Finally, Rh glycoproteins may also function as CO2 transporters. No longer can NH3 transport be considered to occur only through diffusive NH3 movement. Transporter-mediated NH3 movement is fundamental to ammonia metabolism.