Molecular physiology of the Rh ammonia transport proteins

Abstract

Purpose of review 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. Recent findings 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. Summary No longer can NH3 transport be considered to occur only through diffusive NH3 movement. Transporter-mediated NH3 movement is fundamental to ammonia metabolism.

Ammonia excretion in mytilid mussels is facilitated by ciliary beating

“…TAM excretion requires controlled interaction of basolateral uptake and apical release of TAM. In vertebrates, this process is potentially differentially mediated by Rhbg and Rhcg located in basolateral and apical membranes, respectively (Bishop et al, 2010;Weiner and Verlander, 2010), but in invertebrates such as crustaceans and bivalves, so far only one primitive Rh protein has been described (Martin et al, 2011;Zhang et al, 2012). Consequently, an alternative model of vesicular TAM trapping has been suggested for crustaceans involving VHA and the Rh protein located in the membranes of intracellular vesicles (Weihrauch et al, 2002).…”

“…Recent studies have revealed that both passive diffusion of gaseous NH 3 and active NH 4 + transport are facilitated by specialized ion-transporting proteins (Weihrauch et al, 2009;Wright and Wood, 2009;Weiner and Verlander, 2010 and references therein).…”

The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein

“…Ammonium also serves as principal nitrogen source for numerous microorganisms and plants, whereas it is mainly regarded as a blood pH regulator and a cytotoxic compound in mammals [8][9][10] . Three Mep-Amt proteins enable ammonium transport in Saccharomyces cerevisiae 11 .…”

Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion

“…Prominent among these ammonia-transporting proteins are the Rh glycoproteins. Three mammalian Rh glycoproteins have been identified, Rh A glycoprotein, which is expressed specifically in erythroid cells, and the nonerythroid Rh glycoproteins, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), which are expressed widely in ammonia-transporting tissues, including the kidney (29,30,32,33).In the kidney, Rhcg is expressed in the renal distal nephron and collecting duct, from the distal convoluted tubule (DCT) through the inner medullary collecting duct (8,10,20,28), where 60 -80% of final urinary ammonia is secreted. Evidence supporting a critical role for Rhcg in renal ammonia transport includes findings that 1) Rhcg transports NH 3 (reviewed in Ref.…”

“…1 Increasingly, the "traditional" theory of passive NH 3 diffusion and NH 4 ϩ trapping is being replaced by one in which specific membrane proteins transport NH 3 or NH 4 ϩ , enabling facilitated and regulated membrane NH 3 and NH 4 ϩ transport (32,33). Prominent among these ammonia-transporting proteins are the Rh glycoproteins.…”