Structure and permeation mechanism of a mammalian urea transporter

Levin, E.J.; Cao, Yu; Enkavi, Giray; Quick, Matthias; Pan, Yaping; Tajkhorshid, Emad; Zhou, Ming

doi:10.1073/pnas.1207362109

Cited by 68 publications

(143 citation statements)

References 62 publications

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“…We therefore performed sequence based searches for structures homologous to the different subunits of Na 1 NQR using the HHPred server 43 that utilizes hidden Markov models. NqrB was predicted to be structurally homologous to the urea transporter 11 and the structure could be aligned with the transmembrane helices guiding the tracing of the sequence. The low resolution of the experimental map allowed the unambiguous placement of side chains for methionine or tryptophan residues only.…”

Section: Methodsmentioning

confidence: 99%

Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase

Steuber

Vohl

Casutt

et al. 2014

Nature

108

193

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Section: Methodsmentioning

confidence: 99%

Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase

Steuber

Vohl

Casutt

et al. 2014

Nature

108

193

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“…A recent study on the X-ray crystal structure of the UT-B revealed that the UT-B is a homotrimer and each protomer contains a urea conduction pore with a narrow selectivity filter, which has two urea binding sites (74). In contrast, the UT-A gene contains two UT domains in tandem and produces a variety of isoforms (UT-A1 through UT-A6) via alternative splicing (29,59,63,101,103) (Fig.…”

Section: Urea Retention In the Kidney: Urea Transportermentioning

confidence: 99%

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Hyodo

Kakumura

Takagi

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption. Am J Physiol Regul Integr Comp Physiol 307: R1381-R1395, 2014. First published October 22, 2014 doi:10.1152/ajpregu.00033.2014.-For adaptation to highsalinity marine environments, cartilaginous fishes (sharks, skates, rays, and chimaeras) adopt a unique urea-based osmoregulation strategy. Their kidneys reabsorb nearly all filtered urea from the primary urine, and this is an essential component of urea retention in their body fluid. Anatomical investigations have revealed the extraordinarily elaborate nephron system in the kidney of cartilaginous fishes, e.g., the four-loop configuration of each nephron, the occurrence of distinct sinus and bundle zones, and the sac-like peritubular sheath in the bundle zone, in which the nephron segments are arranged in a countercurrent fashion. These anatomical and morphological characteristics have been considered to be important for urea reabsorption; however, a mechanism for urea reabsorption is still largely unknown. This review focuses on recent progress in the identification and mapping of various pumps, channels, and transporters on the nephron segments in the kidney of cartilaginous fishes. The molecules include urea transporters, Na, and aquaporins, which most probably all contribute to the urea reabsorption process. Although research is still in progress, a possible model for urea reabsorption in the kidney of cartilaginous fishes is discussed based on the anatomical features of nephron segments and vascular systems and on the results of molecular mapping. The molecular anatomical approach thus provides a powerful tool for understanding the physiological processes that take place in the highly elaborate kidney of cartilaginous fishes. cartilaginous fish; kidney; osmoregulation; transporters; urea BODY FLUID REGULATION is essential for all organisms to survive in their respective habitats, including freshwater (FW), seawater (SW), and terrestrial environments. It is well known that teleost fish regulate their plasma Na ϩ and Cl Ϫ concentrations and osmolality at levels about one-third of SW. Meanwhile, cartilaginous fishes (sharks, skates, rays, and chimaeras) have adopted a unique osmoregulatory strategy for adaptation to the high-salinity marine environment. Cartilaginous fishes control plasma ions to levels approximately one-half of surrounding SW while they store high concentrations of the nitrogenous compound urea as an osmolyte (the so-called "ureosmotic strategy"). As a result, their body fluids are slightly hyperosmotic to surrounding SW (for instance, plasma osmolality of houndshark is 1,000 mosmol/kg H 2 O in SW of 988 mosmol/kg H 2 O; Ref. 53), and thus cartilaginous fishes do not typically suffer dehydration even in the high-osmolality SW environment. To maintain high concentration of urea in the body, urea production by the ornithine urea cycle (OUC) is essential. Investigations on the OUC enzymes have proved that the liver is the primary organ f...

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“…UT-B has been found in many tissues and species, including human and rodent colon tissues, in erythrocytes and kidney tissue, as well as in ovine and bovine rumen (52). In bovine tissues, the UT-B protein exists as a multimer (30). Previous studies (21,39,41) have shown that changes in dietary nitrogen (N) content causes significant changes in serum urea-N (BUN) concentrations and the entry of urea into the gut.…”

mentioning

confidence: 99%

Short-chain fatty acids and acidic pH upregulate UT-B, GPR41, and GPR4 in rumen epithelial cells of goats

Gui

Yao

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Currently, the mechanism(s) responsible for the regulation of urea transporter B (UT-B) expression levels in the epithelium of the rumen remain unclear. We hypothesized that rumen fermentation products affect ruminal UT-B expression. Therefore, the effects of short-chain fatty acids (SCFA), pH, ammonia, and urea on mRNA and protein levels of UT-B were assayed in primary rumen epithelial cell cultures and in rumen epithelium obtained from intact goats. In vitro, SCFA and acidic pH were found to synergetically stimulate both mRNA and protein expression of UT-B, whereas NH 4Cl decreased mRNA and protein levels of UT-B at pH 6.8. Treatment with urea increased both levels at pH 7.4. When goats received a diet rich in nitrogen (N) and nonfiber carbohydrates (NFC), their rumen epithelium had higher levels of UT-B, and the rumen contained higher concentrations of SCFA and NH 3-N with a lower pH. An increase in plasma urea-N concentration was also observed compared with the plasma of the goats that received a diet low in N and NFC. In a second feeding trial, goats that received a NFC-rich, but isonitrogenous, diet had higher mRNA and protein levels of UT-B, and higher levels of G proteincoupled receptor (GPR) 41 and GPR4, in their rumen epithelium. The ruminal concentrations of SCFA and NH 3-N also increased, while a lower pH was detected. In contrast, the serum urea-N concentrations remained unchanged. These data indicate that ruminal SCFA and pH are key factors, via GPR4 and GPR41, in the dietary regulation of UT-B expression, and they have priority over changes in plasma urea.SCFA and pH; UT-B expression; GPR41; GPR4; rumen epithelial cells; diet RECYCLING OF UREA TO THE MAMMALIAN gut accounts for 20 -30% of liver-synthesized urea that is present in humans (17). In contrast, these levels vary from 10 to 90% in ruminants (21) with feeding strategy (21) and intake of fermentable carbohydrates (22). These characteristics make the ruminant forestomach, especially the rumen, an excellent model for studies of urea entry and regulation in the gut. Urea transport across the rumen epithelium is generally accepted to occur down a concentration gradient from blood to lumen by diffusion through transport proteins, such as urea transporter B (UT-B), or possibly aquaporins. In our laboratory's recent studies, rumen fermentation products, including short-chain fatty acids (SCFA) and ammonia, as well as pH, were found to rapidly modulate UT-B activity (1, 34). It is possible that multiple mechanisms mediate regulation of urea transport, although these mechanisms are not fully characterized. UT-B has been found in many tissues and species, including human and rodent colon tissues, in erythrocytes and kidney tissue, as well as in ovine and bovine rumen (52). In bovine tissues, the UT-B protein exists as a multimer (30). Previous studies (21, 39, 41) have shown that changes in dietary nitrogen (N) content causes significant changes in serum urea-N (BUN) concentrations and the entry of urea into the gut. However, a correlation between N ...

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Structure and permeation mechanism of a mammalian urea transporter

Cited by 68 publications

References 62 publications

Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase

Structure of the V. cholerae Na+-pumping NADH:quinone oxidoreductase

Morphological and functional characteristics of the kidney of cartilaginous fishes: with special reference to urea reabsorption

Short-chain fatty acids and acidic pH upregulate UT-B, GPR41, and GPR4 in rumen epithelial cells of goats

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