The Rh (Rhesus) blood group polypeptides are related to NH4+ transporters

Marini, Anna María; Urrestarazu, Antonio; Beauwens, Renaud; André, Brunó

doi:10.1016/s0968-0004(97)01132-8

Cited by 227 publications

(248 citation statements)

References 19 publications

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“…The selective expression of the human Rhesus (Rh) proteins in cells and tissues involved in such functions supports the notion that they are critically involved in these processes. Sequence comparisons show that the Amt, MEP and Rh proteins represent one large and ubiquitous membrane protein family [24,29].…”

Section: Introductionmentioning

confidence: 99%

Amt/MEP/Rh proteins conduct ammonia

Winkler

2005

Pflugers Arch - Eur J Physiol

110

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The structure determination of the ammonium transport protein AmtB from Escherichia coli strongly indicates that the members of the ubiquitous ammonium transporter/methylamine permease/Rhesus (Amt/ MEP/Rh) protein family are ammonia-conducting channels rather than ammonium ion transporters. The most conserved part of these proteins, apart from the common overall structure with 11 transmembrane helices, is the pore lined by hydrophobic side chains except for two highly conserved histidine residues. A highaffinity ion-binding site specific for ammonium is present at the extracellular pore entry of the Amt/MEP proteins. It is proposed to play an important role in enhancing net transport at very low external ammonium concentrations and to provide discrimination against water. The site is not conserved in the animal Rhesus proteins which are implicated in ammonium homeostasis and saturate at millimolar ammonium concentrations. Many aspects of the biological function of these ammonia channels are still poorly understood and further studies in cellular systems are needed. Likewise, studies with purified, reconstituted Amt/MEP/Rh proteins will be needed to resolve open mechanistic questions and gain a more quantitative understanding of the conduction mechanism in general and for different subfamily representatives.

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Section: Introductionmentioning

confidence: 99%

Amt/MEP/Rh proteins conduct ammonia

Winkler

2005

Pflugers Arch - Eur J Physiol

110

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“…The possibility that Rh (Rhesus) proteins might represent the mammalian members of an Amt/Mep (ammonia transporter/methylammonium permease)/Rh superfamily of ammonium transporters has been raised owing to primary structure homology with Amt/Mep from bacteria, archaea, fungi and plants [1]. In humans, the Rh protein family is composed of five members, RhCE, RhD, RhAG, RhBG and RhCG [2].…”

Section: Introductionmentioning

confidence: 99%

“…The chemical symbols for ammonia (NH 3 ) and ammonium ions (NH 4 + ) are used elsewhere to distinguish between the two forms of ammonium. 1 To whom correspondence should be addressed (email colin@idf.inserm.fr).…”

Section: Introductionmentioning

confidence: 99%

Human Rhesus B and Rhesus C glycoproteins: properties of facilitated ammonium transport in recombinant kidney cells

Zidi-Yahiaoui

Mouro-Chanteloup

d'Ambrosio

et al. 2005

Biochemical Journal

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The mammalian Rh (Rhesus) protein family belongs to the Amt/ Mep (ammonia transporter/methylammonium permease)/Rh superfamily of ammonium transporters. Whereas RhCE, RhD and RhAG are erythroid specific, RhBG and RhCG are expressed in key organs associated with ammonium transport and metabolism. We have investigated the ammonium transport function of human RhBG and RhCG by comparing intracellular pH variation in wild-type and transfected HEK-293 (human embryonic kidney) cells and MDCK (Madin-Darby canine kidney) cells in the presence of ammonium (NH 4 + /NH 3 ) gradients. Stopped-flow spectrofluorimetry analysis, using BCECF [2 ,7 -bis-(2-carboxyethyl)-5(6)-carboxyfluorescein] as a pH-sensitive probe, revealed that all cells submitted to inwardly or outwardly directed ammonium gradients exhibited rapid alkalinization or acidification phases respectively, which account for ammonium movements in transfected and native cells. However, as compared with wildtype cells known to have high NH 3 lipid permeability, RhBGand RhCG-expressing cells exhibited ammonium transport characterized by: (i) a five to six times greater kinetic rateconstant; (ii) a weak temperature-dependence; and (iii) reversible inhibition by mercuric chloride (IC 50: 52 µM). Similarly, when subjected to a methylammonium gradient, RhBG-and RhCGexpressing cells exhibited kinetic rate constants greater than those of native cells. However, these constants were five times higher for RhBG as compared with RhCG, suggesting a difference in substrate accessibility. These results, indicating that RhBG and RhCG facilitate rapid and low-energy-dependent bi-directional ammonium movement across the plasma membrane, favour the hypothesis that these Rh glycoproteins, together with their erythroid homologue RhAG [Ripoche, Bertrand, Gane, Birkenmeier, Colin and Cartron (2005) Proc. Natl. Acad. Sci. U.S.A. 101, 17222-17227] constitute a family of NH 3 channels in mammalian cells.

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“…The first indication of the biological role of Rh proteins came from the discovery of a significant homology, particularly to RhAG, with the methylammonium (MA) permease͞ ammonium transporter (Mep͞Amt) superfamily of ammonium transporters present from bacteria to yeast but absent in vertebrates (8). This discovery was followed by the characterization of two nonerythroid orthologs, RhBG and RhCG (9,10), and the identification of paralogs in a variety of living species, thereby suggesting the conservation of some critical function (reviewed in ref.…”

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confidence: 99%