Cloning and expression of apical membrane water channel of rat kidney collecting tubule

Fushimi, Kiyohide; Uchida, Shinichi; Hara, Yukichi; Hirata, Yukio; Marumo, Fumiaki; Sasaki, Sei

doi:10.1038/361549a0

Cited by 940 publications

(566 citation statements)

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“…In fact, AQP1 knockout mice were found to develop polyuria due to both a defective water reabsorption mechanism in the proximal tubules and a dysfunctional countercurrent mechanism in the inner medulla (26). Other renal AQPs, such as AQP2, AQP3, and AQP4, are all present in the collecting ducts and are directly involved in water reabsorption to produce the final concentrated urine (2,13,14). Very recently, Maeda et al (16) generated AQP7 knockout mice and reported on the phenotype characteristics only in the adipocytes, where AQP7 constitutes a glycerol-releasing pathway without which hypoglycemia occurs after starvation.…”

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confidence: 99%

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice

Sohara¹,

Rai²,

Miyazaki³

et al. 2005

American Journal of Physiology-Renal Physiology

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water channel is known as a member of the aquaglyceroporins, which facilitate the transport of glycerol as well as water. Although AQP7 is abundantly expressed on the apical membrane of the proximal straight tubules in the kidney, the physiological role of AQP7 is still unknown. To investigate this, we generated AQP7 knockout mice. The water permeability of the proximal tubule brush-border membrane measured by the stopped-flow method was slightly but significantly reduced in the AQP7 knockout mice compared with that of wild-type mice (AQP7, 18.0 Ϯ 0.4 ϫ 10 Ϫ3 cm/s vs. wild-type, 20.0 Ϯ 0.3 ϫ 10 Ϫ3 cm/s). Although AQP7 solo-knockout mice did not exhibit a urinary concentrating defect, AQP1/AQP7 double-knockout mice had a reduction in urinary concentrating ability compared with AQP1 soloknockout mice, suggesting that the amount of water reabsorbed through AQP7 in the proximal straight tubules is physiologically substantial. On the other hand, AQP7 knockout mice showed marked glyceroluria (AQP7, 1.7 Ϯ 0.34 mg/ml vs. wild-type, 0.005 Ϯ 0.002 mg/ml). This identified a novel glycerol reabsorption pathway in the proximal straight tubules. In two mouse models of proximal straight tubule injury, the cisplatin-induced acute renal failure (ARF) model and the ischemic ARF model, an increase in urine glycerol was observed (pretreatment, 0.007 Ϯ 0.005 mg/ml; cisplatin, 0.063 Ϯ 0.043 mg/ml; ischemia, 0.076 Ϯ 0.02 mg/ml), suggesting that urine glycerol could be used as a new biomarker for detecting proximal straight tubule injury.

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confidence: 99%

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice

Sohara¹,

Rai²,

Miyazaki³

et al. 2005

American Journal of Physiology-Renal Physiology

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“…The hereditary (congenital) form of NDI is relatively rare, and is known to be caused by mutations in two genes, the arginine vasopressin type 2 receptor (AVPR2) and the water channel aquaporin 2 (AQP2) [1][2][3][4]. These two genes encode two membrane proteins that are oppositely located at the basolateral and apical membranes of the collecting duct principal cells, respectively, and constitute the fundamental components of urine concentrating machinery [5,6].…”

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confidence: 99%

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

et al. 2012

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Background Familial form of nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused by arginine vasopressin type 2 receptor (AVPR2) or water channel aquaporin 2 (AQP2) gene mutations. It is speculated that 90 % of NDI families carry disease-causing mutations in AVPR2 and 10 % carry the mutations in AQP2; however, these percentages have not been supported by actual data. It is also unknown whether these percentages vary in different ethnic groups. Methods Gene mutation analyses were performed for 78 Japanese NDI families. All exons and intron-exon boundaries of the AVPR2 and AQP2 genes were directly sequenced. Results A total of 62 families (79 %) carried diseasecausing mutations in AVPR2, while nine families (12 %) carried mutations in AQP2. We identified 22 novel putatively disease-causing mutations (19 in AVPR2 and 3 in AQP2). Regarding AVPR2, 52 disease-causing mutations were identified. Among them, missense mutations were most common (54 %), followed by deletion mutations. In the 64 women who had monoallelic disease-causing AVPR2 mutations, 16 (25 %) had NDI symptoms, including 4 complete NDI subjects. Regarding AQP2, 9 disease-causing mutations were identified in nine families. Two missense mutations and one deletion mutation showed a recessive inheritance, while one missense mutation and five small deletion mutations in the C-terminus of AQP2 showed a dominant inheritance.Conclusions Most Japanese NDI families carry diseasecausing mutations in AVPR2 and 12 % carry mutations in AQP2. A total of 22 novel putatively disease-causing mutations were identified. The relatively high occurrence of symptomatic carriers of AVPR2 mutations needs attention.

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“…15,16 When living cells were incubated with fluorescently labeled transferrin to label endosomes ( Figure 4B) and were subsequently subjected to confocal immunofluorescence microscopy to detect AQP2 and late endosomes/lysosomes with an antibody against LAMP 1 ( Figure 4D), this triple labeling protocol provided evidence for co-distribution of wt AQP2 with a limited number (ϳ20 to 30%) of transferrin-loaded endosomes ( Figure 4C). However, the limited x-y resolution of confocal immunofluorescence (Յ200 nm) allows no statement that wt AQP2 actually co-localizes with endosomes.…”

Section: Intracellular Distribution Of Wild-type and Mutant Aqp2mentioning

confidence: 99%

“…12 AQP2 belongs to the large family of AQPs, 13,14 and is a 29-kd polytope membrane protein that contains a single N-glycosylation site and two phosphorylation sites, and is present in the principal cells of renal collecting ducts. 15,16 In states of hypernatremia or hypovolemia, translocation of phosphorylated AQP2 homotetramers from vesicles to the apical plasma membrane of the principal cells is triggered by a signal transduction cascade induced by arginine-vasopressin. 16 -18 Alike to normal human kidney, 19 wild-type (wt) AQP2, when expressed in Xenopus oocytes 20,21 or various mammalian cell lines, 18,22 existed as a nonglycosylated 29-kd form.…”

Section: Mutations In the Water Channel Aquaporin-2 (Aqp2) Can Cause mentioning

confidence: 99%

The Proteasome Is Involved in the Degradation of Different Aquaporin-2 Mutants Causing Nephrogenic Diabetes Insipidus

Hirano

Zuber

Roth

et al. 2003

The American Journal of Pathology

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Mutations in the water channel aquaporin-2 (AQP2) can cause congenital nephrogenic diabetes insipidus. To reveal the possible involvement of the protein quality control system in processing AQP2 mutants, we created an in vitro system of clone 9 hepatocytes stably expressing endoplasmic reticulum-retained T126M AQP2 and misrouted E258K AQP2 as well as wild-type AQP2 and studied their biosynthesis, degradation, and intracellular distribution. Mutant and wild-type AQP2 were synthesized as 29-kd nonglycosylated and 32-kd core-glycosylated forms in the endoplasmic reticulum. The wild-type AQP2 had a t 1/2 of 4.6 hours. Remarkable differences in the degradation kinetics were observed for the glycosylated and nonglycosylated T126M AQP2 (t 1/2 ‫؍‬ 2.0 hours versus 0.9 hours). Moreover, their degradation was depending on proteasomal activity as demonstrated in inhibition studies. Degradation of E258K AQP2 also occurred rapidly (t 1/2 ‫؍‬ 1.8 hours) but in a proteasome-and lysosome-dependent manner. By triple confocal immunofluorescence microscopy misrouting of E258K to lysosomes via the Golgi apparatus could be demonstrated. Notwithstanding the differences in degradation kinetics and subcellular distribution such as endoplasmic reticulum-retention and misrouting to lysosomes, both T126M and E258K AQP2 were efficiently degraded. This implies the involvement of different protein quality control processes in the processing of these AQP2 mutants. The endoplasmic reticulum (ER) represents a site of quality control of glycoprotein folding. 1,2 Misfolded glycoproteins are recognized and retained by the concerted action of chaperones, lectins, and modifying enzymes such as UDP-glucose:glycoprotein glucosyltransferase and glucosidase II. 3 Glycoproteins failing to achieve their correct conformation might become retrotranslocated to the cytosol 4 and degraded by the ubiquitin-proteasome pathway, a process referred to as ER-associated protein degradation. [5][6][7] Quality control of protein folding is of importance in congenital diseases caused by point mutations that result in the synthesis of misfolded glycoproteins. 8 Mutations in the water channel aquaporin-2 (AQP2) can cause nephrogenic diabetes insipidus (NDI), in which patients are unable to concentrate urine in response to the anti-diuretic hormone arginine-vasopressin. 9 -11 If not corrected, this defect results in a deregulated whole-body water homeostasis that is accompanied by various symptoms of dehydration. 12 AQP2 belongs to the large family of AQPs, 13,14 and is a 29-kd polytope membrane protein that contains a single N-glycosylation site and two phosphorylation sites, and is present in the principal cells of renal collecting ducts. 15,16 In states of hypernatremia or hypovolemia, translocation of phosphorylated AQP2 homotetramers from vesicles to the apical plasma membrane of the principal cells is triggered by a signal transduction cascade induced by arginine-vasopressin. 16 -18 Alike to normal human kidney, 19 wild-type (wt) AQP2, when expressed in Xenopus ooc...

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Cloning and expression of apical membrane water channel of rat kidney collecting tubule

Cited by 940 publications

References 19 publications

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice

Defective water and glycerol transport in the proximal tubules of AQP7 knockout mice

Hereditary nephrogenic diabetes insipidus in Japanese patients: analysis of 78 families and report of 22 new mutations in AVPR2 and AQP2

The Proteasome Is Involved in the Degradation of Different Aquaporin-2 Mutants Causing Nephrogenic Diabetes Insipidus

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