The Rh protein family: gene evolution, membrane biology, and disease association

Huang, Cheng‐Han; Ye, Mao

doi:10.1007/s00018-009-0217-x

Cited by 45 publications

(44 citation statements)

References 147 publications

(252 reference statements)

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“…6) groups the Rhag, Rhbg, and Rhcg clusters closely together, while the Rhp group remains further away, and the nonammonia-transporting Rh30 cluster is situated furthest away. The ML-tree positioning of the microbe N. europaea Rh protein, a member of the prokaryotic Rh proteins, which are suggested to be a common ancestor from which eukaryotic Rh proteins derive (23), implies that the primitive invertebrate Rhp proteins are a sister group to the possibly more derived vertebrate ammonia-transporting Rhag, Rhbg, and Rhcg. While the ammonia-transporting capabilities of the vertebrate Rh proteins have received considerable attention (69), the role of Rhp genes in ammonia transport has been poorly studied.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of ammonia excretion in the freshwater leechNephelopsis obscura: characterization of a primitive Rh protein and effects of high environmental ammonia

Quijada-Rodriguez

Treberg

Weihrauch

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Remarkably little is known about nitrogenous excretion in freshwater invertebrates. In the current study, the nitrogen excretion mechanism in the carnivorous ribbon leech, Nephelopsis obscura, was investigated. Excretion experiments showed that the ribbon leech is ammonotelic, excreting 166.0 ± 8.6 nmol·grams fresh weight (gFW)−1·h−1 ammonia and 14.7 ± 1.9 nmol·gFW−1·h−1 urea. Exposure to high and low pH hampered and enhanced, respectively, ammonia excretion rates, indicating an acid-linked ammonia trapping mechanism across the skin epithelia. Accordingly, compared with body tissues, the skin exhibited elevated mRNA expression levels of a newly identified Rhesus protein and at least in tendency the Na+/K+-ATPase. Pharmacological experiments and enzyme assays suggested an ammonia excretion mechanism that involves the V-ATPase, Na+/K+-ATPase, and carbonic anhydrase, but not necessarily a functional microtubule system. Most importantly, functional expression studies of the identified Rh protein cloned from leech skin tissue revealed an ammonia transport capability of this protein when expressed in yeast. The leech Rh-ammonia transporter (NoRhp) is a member of the primitive Rh protein family, which is a sister group to the common ancestor of vertebrate ammonia-transporting Rh proteins. Exposure to high environmental ammonia (HEA) caused a new adjustment of body ammonia, accompanied with a decrease in NoRhp and Na+/K+-ATPase mRNA levels, but unaltered ammonia excretion rates. To our knowledge, this is only the second comprehensive study regarding the ammonia excretion mechanisms in a freshwater invertebrate, but our results show that basic processes of ammonia excretion appear to also be comparable to those found in freshwater fish, suggesting an early evolution of ionoregulatory mechanisms in freshwater organisms.

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Section: Discussionmentioning

confidence: 99%

Mechanism of ammonia excretion in the freshwater leechNephelopsis obscura: characterization of a primitive Rh protein and effects of high environmental ammonia

Quijada-Rodriguez

Treberg

Weihrauch

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Six clusters of the Rh family have been defined by an extensive molecular phylogenetic analysis (49,50). In houndshark, Rhp2 was found to distribute in the 2nd and 4th loops of nephron (84).…”

Section: Urea Synthesis In the Kidneymentioning

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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“…There may well be other roles for Rh proteins. Notably, the Rhbg and Rhcg2 proteins in Magadi tilapia are unusual, with only 10 transmembrane domains, rather than the 12 that are considered normal (Huang and Ye, 2010). Far simpler changes such as a mere two amino acid substitution can change a mammalian RhAG glycoprotein into a cation-selective channel (Bruce et al, 2009).…”

Section: The Role Of Rh Proteins In Magadi Tilapiamentioning

confidence: 99%

“…Far simpler changes such as a mere two amino acid substitution can change a mammalian RhAG glycoprotein into a cation-selective channel (Bruce et al, 2009). In mammals, normal and mutated Rh proteins have been implicated in infertility, depression, tumour suppression, migraines and even HCO 3 -transport (Huang and Ye, 2010). The latter is worthy of future investigation, because the Magadi tilapia must actively excrete HCO 3 -across its gills .…”

Section: The Role Of Rh Proteins In Magadi Tilapiamentioning

confidence: 99%

Rh proteins and NH4+-activated Na+-ATPase in the Magadi tilapia (Alcolapia grahami), a 100% ureotelic teleost fish

Wood

Nawata

Wilson³

et al. 2013

Journal of Experimental Biology

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SUMMARYThe small cichlid fish Alcolapia grahami lives in Lake Magadi, Kenya, one of the most extreme aquatic environments on Earth (pH 10, carbonate alkalinity ~300mequivl −1). The Magadi tilapia is the only 100% ureotelic teleost; it normally excretes no ammonia. This is interpreted as an evolutionary adaptation to overcome the near impossibility of sustaining an NH 3 diffusion gradient across the gills against the high external pH. In standard ammoniotelic teleosts, branchial ammonia excretion is facilitated by Rh glycoproteins, and cortisol plays a role in upregulating these carriers, together with other components of a transport metabolon, so as to actively excrete ammonia during high environmental ammonia (HEA) exposure. In Magadi tilapia, we show that at least three Rh proteins (Rhag, Rhbg and Rhcg2) are expressed at the mRNA level in various tissues, and are recognized in the gills by specific antibodies. During HEA exposure, plasma ammonia levels and urea excretion rates increase markedly, and mRNA expression for the branchial urea transporter mtUT is elevated. Plasma cortisol increases and branchial mRNAs for Rhbg, Rhcg2 and Na Supplementary material available online at

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The Rh protein family: gene evolution, membrane biology, and disease association

Cited by 45 publications

References 147 publications

Mechanism of ammonia excretion in the freshwater leechNephelopsis obscura: characterization of a primitive Rh protein and effects of high environmental ammonia

Mechanism of ammonia excretion in the freshwater leechNephelopsis obscura: characterization of a primitive Rh protein and effects of high environmental ammonia

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

Rh proteins and NH4+-activated Na+-ATPase in the Magadi tilapia (Alcolapia grahami), a 100% ureotelic teleost fish

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