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Mark A. Knepper - One of the best experts on this subject based on the ideXlab platform.
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Vasopressin-induced serine 269 phosphorylation reduces Sipa1l1 (signal-induced proliferation-associated 1 like 1)-mediated Aquaporin-2 endocytosis.
The Journal of biological chemistry, 2017Co-Authors: Po-jen Wang, Shu-ting Lin, Shao-hsuan Liu, Kuang-ting Kuo, Chun-hua Hsu, Mark A. KnepperAbstract:The abundance of integral membrane proteins in the plasma membrane is determined by a dynamic balance between exocytosis and endocytosis, which can often be regulated by physiological stimuli. Here, we describe a mechanism that accounts for the ability of the peptide hormone vasopressin to regulate water excretion via a phosphorylation-dependent modulation of the PDZ domain-ligand interaction involving the water channel protein Aquaporin-2. We discovered that the PDZ domain-containing protein Sipa1l1 (signal-induced proliferation-associated 1 like 1) binds to the cytoplasmic PDZ-ligand motif of Aquaporin-2 and accelerates its endocytosis in the absence of vasopressin. Vasopressin-induced Aquaporin-2 phosphorylation within the type I PDZ-ligand motif disrupted the interaction, in association with reduced Aquaporin-2 endocytosis and prolonged plasma membrane Aquaporin-2 retention. This phosphorylation-dependent alteration in the PDZ domain-ligand interaction was explained by 3D structural models, which showed a hormone-regulated mechanism that controls osmotic water transport and systemic water balance in mammals.
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Comprehensive database of human E3 ubiquitin ligases: application to Aquaporin-2 regulation.
Physiological genomics, 2016Co-Authors: Barbara Medvar, Trairak Pisitkun, Viswanathan Raghuram, Abhijit Sarkar, Mark A. KnepperAbstract:Aquaporin-2 (AQP2) is regulated in part via vasopressin-mediated changes in protein half-life that are in turn dependent on AQP2 ubiquitination. Here we addressed the question, “What E3 ubiquitin l...
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Vasopressin and the regulation of Aquaporin-2
Clinical and Experimental Nephrology, 2013Co-Authors: Justin L. L. Wilson, Carlos A. Miranda, Mark A. KnepperAbstract:Water excretion is regulated in large part through the regulation of osmotic water permeability of the renal collecting duct epithelium. Water permeability is controlled by vasopressin through regulation of the water channel, Aquaporin-2 (AQP2). Two processes contribute: (1) regulation of AQP2 trafficking to the apical plasma membrane; and (2) regulation of the total amount of the AQP2 protein in the cells. Regulation of AQP2 abundance is defective in several water-balance disorders, including many polyuric disorders and the syndrome of inappropriate antidiuresis. Here we review vasopressin signaling in the renal collecting duct that is relevant to the two modes of water permeability regulation.
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Aquaporin-2 in the "-omics" era.
The Journal of biological chemistry, 2009Co-Authors: Jason D. Hoffert, Chung-lin Chou, Mark A. KnepperAbstract:Vasopressin controls renal water excretion largely through actions to regulate the water channel Aquaporin-2 in collecting duct principal cells. Our knowledge of the mechanisms involved has increased markedly in recent years with the advent of methods for large-scale systems-level profiling such as protein mass spectrometry, yeast two-hybrid analysis, and oligonucleotide microarrays. Here we review this progress.
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Serine 269 phosphorylated Aquaporin-2 is targeted to the apical membrane of collecting duct principal cells
Kidney international, 2008Co-Authors: Hanne B. Moeller, Mark A. Knepper, Robert A. FentonAbstract:Trafficking of the water channel Aquaporin-2 to the apical plasma membrane of the collecting duct is mediated by arginine vasopressin, rendering the cell permeable to water. We recently identified a novel form of Aquaporin-2 that is phosphorylated at serine-269 (pS269-AQP2). Using antibodies specific for this form of the water channel, we detected rat and mouse pS269-AQP2 in the connecting tubule and throughout the collecting duct system. Using confocal immunofluorescence microscopy with organelle-specific markers and immunogold electron microscopy, we found that pS269-AQP2 was found only on the apical plasma membrane of principal cells. In vasopressin-deficient Brattleboro rats, pS269-AQP2 was undetectable but dramatically increased in abundance after these rats were treated with [deamino-Cys-1, d-Arg-8]vasopressin (dDAVP). This increase occurred only at the apical plasma membrane, even after long-term dDAVP treatment. Following dDAVP there was a time-dependent redistribution of total Aquaporin-2 from predominantly intracellular vesicles to the apical plasma membrane, clathrin-coated vesicles, early endosomal compartments, and lysosomes. However, pS269-AQP2 was found only on the apical plasma membrane at any time. Our results show that S269 phosphorylated Aquaporin-2 is exclusively associated with the apical plasma membrane, where it escapes endocytosis to remain at the cell surface.
Peter M. T. Deen - One of the best experts on this subject based on the ideXlab platform.
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ndfip1 the missing adaptor for Aquaporin 2 regulation by nedd4 and nedd4l lb723
The FASEB Journal, 2014Co-Authors: Theun De Groot, Christiane Trimpert, Dennis Van Den Berg, Daniel J Wesche, Victoria S S Wong, Igor Stagljar, Peter M. T. DeenAbstract:The Aquaporin 2 (AQP2) water channel in collecting duct principal cells is essential for renal water reabsorption. Fine-tuning of its expression in the apical membrane is critical for reabsorption ...
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Lithium reduces Aquaporin-2 transcription independent of prostaglandins
American journal of physiology. Cell physiology, 2011Co-Authors: Marleen L. A. Kortenoeven, Horst Schweer, Rik Cox, Jack F.m. Wetzels, Peter M. T. DeenAbstract:Vasopressin (AVP)-stimulated translocation and transcription of Aquaporin-2 (AQP2) water channels in renal principal cells is essential for urine concentration. Twenty percent of patients treated w...
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Aquaporin 2 Mutations in Nephrogenic Diabetes Insipidus
Seminars in nephrology, 2008Co-Authors: Anne J.m. Loonen, Nine V.a.m. Knoers, Carel H. Van Os, Peter M. T. DeenAbstract:Water reabsorption in the renal collecting duct is regulated by the antidiuretic hormone vasopressin (AVP). When the vasopressin V2 receptor, present on the basolateral site of the renal principal cell, becomes activated by AVP, Aquaporin-2 (AQP2) water channels will be inserted in the apical membrane, and in this fashion, water can be reabsorbed from the pro-urine into the interstitium. The essential role of the vasopressin V2 receptor and AQP2 in the maintenance of body water homeostasis became clear when it was shown that mutations in their genes cause nephrogenic diabetes insipidus, a disorder in which the kidney is unable to concentrate urine in response to AVP. This review describes the current knowledge on AQP2 mutations in nephrogenic diabetes insipidus.
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Routing of the Aquaporin-2 water channel in health and disease.
European journal of cell biology, 2000Co-Authors: Peter M. T. Deen, B.w.m. Van Balkom, Erik-jan KamsteegAbstract:Summary The identification of the first water channel in 1991 opened up a new field in cell biology and physiology that significantly increased our understanding of mammalian water balance regulation. Since then, nine other mammalian Aquaporins have been identified. Although the physiological significance of many Aquaporins is still to be elucidated, it has been clearly established for Aquaporin-2. This water channel, which is expressed in the renal collecting duct, is redistributed to the apical membrane in response to a intracellular signaling cascade, initiated by binding of the antidiuretic hormone vasopressin to its receptor. In pathological conditions, characterized by a reduced reabsorption of water from urine, the expression of Aquaporin-2 and the apical targeting is always found to be reduced or absent. Naturally-occurring AQP2 mutations that cause Nephrogenic Diabetes Insipidus, a disease in which the kidney is unable to concentrate urine in response to vasopressin, are extreme examples of this condition. In contrast, in diseases with increased renal water uptake, total and apical membrane expression of Aquaporin-2 is increased. Since most Aquaporins, including Aquaporin-2, are considered to be constitutively open channels, much attention has been given to the regulation of the shuttling of Aquaporin-2 to the apical membrane. This review focusses on the present understanding of the regulation of the routing of Aquaporin-2 in collecting duct cells and the misrouting of Aquaporin-2 mutants in Nephrogenic Diabetes Insipidus.
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Physiology and pathophysiology of the Aquaporin-2 water channel
Current Opinion in Nephrology and Hypertension, 1998Co-Authors: Peter M. T. Deen, Nine V.a.m. KnoersAbstract:: Aquaporins are integral membrane proteins, which function as specialized water channels to facilitate the passage of water through the cell membrane. In mammals six different Aquaporins have been identified up to now, four of which (Aquaporin-1 to Aquaporin-4) are expressed in the kidney. Because of its importance for normal water homeostasis and its involvement in many water balance disorders, Aquaporin-2, the predominant vasopressin-regulated water channel of the renal collecting duct, is discussed in detail.
Sei Sasaki - One of the best experts on this subject based on the ideXlab platform.
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Aquaporin-2 protein dynamics within the cell.
Current opinion in nephrology and hypertension, 2007Co-Authors: Sei Sasaki, Yumi NodaAbstract:Purpose of review Aquaporin-2 is an Aquaporin water channel protein present at the apical membrane of kidney collecting duct cells and plays a key role in urine concentrating ability. Like other membrane proteins, Aquaporin-2 undergoes dynamic processes within the cells: synthesized, targeted to the subapical region, exocytosed to the apical membrane, endocytosed, recycled and finally degraded. The understanding of the molecular and cellular mechanisms of these events is advancing rapidly, and recent new findings characterizing such processes are reviewed. Recent findings Hypertonicity itself stimulates Aquaporin-2 expression through the tonicity-responsive enhancer and its transcription factors. Gene targeted mouse models for human nephrogenic diabetes insipidus show the importance of the C-terminus of Aquaporin-2 in apical sorting and provide mechanistic insights. Evidence for the importance of actin cytoskelton in exocytosis of Aquaporin-2 to the apical membrane is accumulating. Actin and other proteins bind to Aquaporin-2 and make a multiprotein complex. New proteomic analyses indicate the involvement of a large series of proteins in Aquaporin-2 dynamics. Summary The protein-level understanding of Aquaporin-2 dynamics has advanced considerably over the past few years, and continuing studies will open a new way in developing new manoeuvres or drugs to manipulate kidney water homeostasis.
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Trafficking mechanism of water channel Aquaporin-2.
Biology of the cell, 2005Co-Authors: Yumi Noda, Sei SasakiAbstract:Targeted positioning of the water channel AQP2 (Aquaporin-2) strictly regulates body water homoeostasis. Trafficking of AQP2 to the apical membrane is critical for the reabsorption of water in renal collecting ducts. In addition to the cAMP-mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other signalling cascades can also induce this sorting. Recently, AQP2-binding proteins which could regulate this trafficking have been discovered; SPA-1 (signal-induced proliferation-associated gene-1), a GAP (GTPase-activating protein) for Rap1, and the cytoskeletal protein actin. This review summarizes recent advances related to the trafficking mechanisms of AQP2.
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Vasopressin-dependent upregulation of Aquaporin-2 gene expression in glucocorticoid-deficient rats.
American journal of physiology. Renal physiology, 2000Co-Authors: Takako Saito, Sei Sasaki, San-e Ishikawa, Fumiko Ando, Minori Higashiyama, Shoichiro Nagasaka, Toshikazu SaitoAbstract:We determined alterations in renal Aquaporin-2 (AQP2) gene expression in association with impaired water excretion in glucocorticoid-deficient rats. After adrenalectomy, Sprague-Dawley rats were ad...
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Suppressed urinary excretion of Aquaporin-2 in an infant with primary polydipsia.
Pediatric nephrology (Berlin Germany), 2000Co-Authors: Tohru Matsumoto, Sei Sasaki, Kazuo Kanno, M Takeya, S Takuwa, E Hiquchi, A Fujimatsu, H Maeshiro, Yuhei Ito, Hirohisa KatoAbstract:We observed severe overhydration in an 18-month-old Japanese girl with primary polydipsia. The secretion of antidiuretic hormone (ADH) was decreased, and urinary excretion of Aquaporin-2, a vasopressin-sensitive water channel protein, was suppressed under basal conditions, but the response of Aquaporin-2 to ADH was essentially preserved. These findings suggest that the water channel itself was intact and that overhydration resulting from polydipsia was responsible for the decreased ADH secretion and suppression of the water channel protein.
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Functional analysis of Aquaporin-2 mutants associated with nephrogenic diabetes insipidus by yeast expression
The American journal of physiology, 1999Co-Authors: Itsuki Shinbo, Sei Sasaki, Kiyohide Fushimi, Michihiro Kasahara, Kazushi Yamauchi, Fumiaki MarumoAbstract:Mutations of Aquaporin-2 (AQP2) vasopressin water channel cause nephrogenic diabetes insipidus (NDI). It has been suggested that impaired routing of AQP2 mutants to the plasma membrane causes the d...
Dennis Brown - One of the best experts on this subject based on the ideXlab platform.
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Aquaporin-2 Inhibitors: Fishing in the Chemical Pool
Journal of the American Society of Nephrology : JASN, 2013Co-Authors: Dennis BrownAbstract:The critical contribution of Aquaporin-2 (AQP) to water homeostasis in mammals is highlighted by the severe concentrating defects seen in humans with mutations in the AQP2 gene and in mice that are AQP2 null or have loss-of-function mutations in AQP2 .[1][1],[2][2] The role of the antidiuretic
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Phosphorylation events and the modulation of Aquaporin 2 cell surface expression
Current opinion in nephrology and hypertension, 2008Co-Authors: Dennis Brown, Udo Hasler, Paula Nunes, Richard BouleyAbstract:Purpose of reviewThis review highlights the role of phosphorylation in the trafficking and targeting of Aquaporin 2. Current knowledge will be put into the context of modulating the cell surface expression of Aquaporin 2 by vasopressin in renal epithelial cells, which is critical for regulation of u
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Methyl-β-cyclodextrin induces vasopressin-independent apical accumulation of Aquaporin-2 in the isolated, perfused rat kidney
American journal of physiology. Renal physiology, 2006Co-Authors: Leileata M. Russo, Mary Mckee, Dennis BrownAbstract:Vasopressin increases urine concentration by stimulating plasma membrane accumulation of Aquaporin-2 (AQP2) in collecting duct principal cells, allowing bulk water flow across the collecting duct f...
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The ins and outs of Aquaporin-2 trafficking.
American journal of physiology. Renal physiology, 2003Co-Authors: Dennis BrownAbstract:This review outlines recent advances related to the molecular mechanisms and pathways of Aquaporin-2 (AQP2) water channel trafficking. AQP2 is a fascinating protein, whose sorting signals can be in...
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Aquaporin 2 is a vasopressin independent constitutive apical membrane protein in rat vas deferens
American Journal of Physiology-cell Physiology, 2000Co-Authors: Anna Stevens, Richard Bouley, Sylvie Breton, Corinne E Gustafson, Raoul D Nelson, Donald E Kohan, Dennis BrownAbstract:Aquaporin 2 (AQP2), the vasopressin-regulated water channel, was originally identified in renal collecting duct principal cells. However, our recent description of AQP2 in the vas deferens indicate...
Nine V.a.m. Knoers - One of the best experts on this subject based on the ideXlab platform.
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Aquaporin 2 Mutations in Nephrogenic Diabetes Insipidus
Seminars in nephrology, 2008Co-Authors: Anne J.m. Loonen, Nine V.a.m. Knoers, Carel H. Van Os, Peter M. T. DeenAbstract:Water reabsorption in the renal collecting duct is regulated by the antidiuretic hormone vasopressin (AVP). When the vasopressin V2 receptor, present on the basolateral site of the renal principal cell, becomes activated by AVP, Aquaporin-2 (AQP2) water channels will be inserted in the apical membrane, and in this fashion, water can be reabsorbed from the pro-urine into the interstitium. The essential role of the vasopressin V2 receptor and AQP2 in the maintenance of body water homeostasis became clear when it was shown that mutations in their genes cause nephrogenic diabetes insipidus, a disorder in which the kidney is unable to concentrate urine in response to AVP. This review describes the current knowledge on AQP2 mutations in nephrogenic diabetes insipidus.
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Physiology and pathophysiology of the Aquaporin-2 water channel
Current Opinion in Nephrology and Hypertension, 1998Co-Authors: Peter M. T. Deen, Nine V.a.m. KnoersAbstract:: Aquaporins are integral membrane proteins, which function as specialized water channels to facilitate the passage of water through the cell membrane. In mammals six different Aquaporins have been identified up to now, four of which (Aquaporin-1 to Aquaporin-4) are expressed in the kidney. Because of its importance for normal water homeostasis and its involvement in many water balance disorders, Aquaporin-2, the predominant vasopressin-regulated water channel of the renal collecting duct, is discussed in detail.
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Vasopressin Type-2 Receptor and Aquaporin-2 Water Channel Mutants in Nephrogenic Diabetes Insipidus
The American journal of the medical sciences, 1998Co-Authors: Peter M. T. Deen, Nine V.a.m. KnoersAbstract:The regulation of water excretion by the kidney is one of the few physiologic processes that are prominent in everyday life. This process predominantly occurs in renal collecting duct cells, where transcellular water reabsorption is induced after binding of the pituitary hormone arginine-vasopressin to its vasopressin type-2 receptor and the subsequent insertion of Aquaporin-2 (AQP2) water channels in the apical membrane of these cells. Removal of the hormone triggers endocytosis of AQP2 and restores the water-impermeable state of the collecting duct cells. Nephrogenic diabetes insipidus is characterized by the inability of the kidney to concentrate urine in response to vasopressin; the vasopressin type-2 receptor and the AQP2 water channel have both been shown to be involved in this disease. This article focuses on mutations in the vasopressin V2 receptor and Aquaporin-2 water channel identified in nephrogenic diabetes insipidus patients, and on the effects of these mutations on the transport and function of these proteins upon expression in cell systems.
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Autosomal Recessive Nephrogenic Diabetes Insipidus Caused by an Aquaporin-2 Mutation*
The Journal of clinical endocrinology and metabolism, 1997Co-Authors: Z. Hochberg, A.f. Van Lieburg, L. Even, Barry M. Brenner, Naomi Lanir, B.a. Van Oost, Nine V.a.m. KnoersAbstract:Vasopressin V2 receptors, expressed from an x-chromosomal gene, are involved in antidiuresis, but also in release of coagulation factor VIII and von Willebrand factor (vWF). The present study describes autosomal recessive nephrogenic diabetes insipidus (NDI) in a large cluster of patients in Israel's Lower-Galilee. Evidence for an intact V2 receptor was concluded by their normal increase in factor VIII and vWF after desmopressin infusion. Thus, in these patients a defect in the pathway beyond the V2 receptor was suspected. The recent cloning of the human Aquaporin-2 gene enabled us to test this gene as a candidate for such a postreceptor defect. Direct sequencing of the Aquaporin-2 gene revealed a G298T substitution causing a Gly100Stop nonsense mutation in the third transmembrane region. Because this putative disease-causing mutation was identified in index patients of different families, we suggest that all patients are descendants of a common ancestor. Thus, this new entity is characterized by an autosomal recessive NDI. The differential response of clotting factors and urine osmolality to desmopressin may provide a simple tool for clinical diagnosis of a V2-postreceptor defect. The early stop-codon of Aquaporin-2 results in complete resistance to vasopressin antidiuretic effect.
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requirement of human renal water channel Aquaporin 2 for vasopressin dependent concentration of urine
Science, 1994Co-Authors: P.m.t. Deen, Nine V.a.m. Knoers, M Verdijk, B Wieringa, Leo A H Monnens, B A Van OostAbstract:Concentration of urine in mammals is regulated by the antidiuretic hormone vasopressin. Binding of vasopressin to its V2 receptor leads to the insertion of water channels in apical membranes of principal cells in collecting ducts. In nephrogenic diabetes insipidus (NDI), the kidney fails to concentrate urine in response to vasopressin. A male patient with an autosomal recessive form of NDI was found to be a compound heterozygote for two mutations in the gene encoding Aquaporin-2, a water channel. Functional expression studies in Xenopus oocytes revealed that each mutation resulted in nonfunctional water channel proteins. Thus, Aquaporin-2 is essential for vasopressin-dependent concentration of urine.