Rhesus factors and ammonium: a function in efflux?

Abstract

Completion of fungal, plant and human genomes paved the way to the identification of erythrocytic rhesus proteins and their kidney homologs as ammonium transporters.

Figure 1

Models for NH₃ and NH₄⁺ transport. (a) Channel- or carrier-mediated uniport for NH₄⁺. Both concentration gradient and transmembrane voltage influence the direction of transport. A firmly established example of such NH₄⁺ transport is through potassium channels. (b) NH₃/H⁺ co-transporter. Driven by the pH gradient and transmembrane voltage, ammonia may be taken up against a concentration gradient for NH₃. The electrochemical situation is similar as for NH₄⁺ uniport in (a). (c) Carrier-mediated antiport for NH₄⁺ with unknown secondary substrate(s), for example, cation C⁺. If both substrates are univalent only the concentration gradients determine the direction of transport. In the kidney, C⁺ could be sodium. (d) Channel- or carrier-mediated uniport for NH₃. Independent of the membrane potential, ammonia will equilibrate along its concentration gradient (depending on the external and internal pH). A net inflow of ammonium into the cytoplasm will depend on ammonium metabolism, which acts as a sink for NH₃/NH₄⁺.

Figure 2

A phylogenetic tree of Mep, AMT and Rh-like proteins. Rh and AMT/Mep proteins are found in bacteria, archaebacteria and eukaryotes. The amino acid sequence alignment was created using the program ClustalW, and phylogenetic analysis was done using the program PAUP 4.0b4a. Highly variable amino- and carboxy-terminal sequences were removed before analysis. Only one archaebacterial sequence (Mj, Methanococchus janaschii) and those prokaryotic sequences that have been analyzed for ammonia transport have been included: Ec, Escherichia coli; Sy, Synechocystis sp.; Ac, Azorhizobium caulinodans; Av, Azotobacter vinelandii; Ab, Azospirillum brasilense; Re, Rhizobium etli; Cg, Corynebacterium glutamicum. With the exception of human (Hs, Homo sapiens), slime mold (Dd, Dictyostelium discoideum), marine sponge (Gc, Geodia cydonium), and zebrafish (Danio rerio), only eukaryotic sequences from fully sequenced organisms (Dm, Drosophila melanogaster (fruit fly); Ce, Caenorhabditis elegans (nematode); At, Arabidopsis thaliana (plant); Sc, Saccharomyces cerevisiae (yeast)) have been included.