Source:http://linkedlifedata.com/resource/pubmed/id/19458121
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2009-7-24
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| pubmed:abstractText |
Aquaporin-2 (AQP2) is a water channel responsible for the final water reabsorption in renal collecting ducts. Alterations in AQP2 function induce nephrogenic diabetes insipidus (NDI), a condition characterized by severe polyuria and polydipsia. Three patients affected with severe NDI, who were compound heterozygous for the AQP2 mutations D150E and G196D, are presented here along with a mildly affected D150E homozygous patient from another family. Using Xenopus oocytes as an expression system, these two mutations (G196D and D150E) were compared with the wild-type protein (AQP2-wt) for functional activity (water flux analysis), protein maturation, and plasma membrane targeting. AQP2-wt induces a major increase in water permeability (P(f) = 47.4 +/- 12.2 x 10(-4) cm/s) whereas D150E displays intermediate P(f) values (P(f) = 12.5 +/- 3.0 x 10(-4) cm/s) and G196D presents no specific water flux, similar to controls (P(f) = 2.1 +/- 0.8 x 10(-4) cm/s and 2.2 +/- 0.7 x 10(-4) cm/s, respectively). Western blot and immunocytochemical evaluations show protein targeting that parallels activity levels with AQP2-wt adequately targeted to the plasma membrane, partial targeting for D150E, and complete sequestration of G196D within intracellular compartments. When coinjecting AQP2-wt with mutants, no (AQP2-wt + D150E) or partial (AQP2-wt + G196D) reduction of water flux were observed compared with AQP2-wt alone, whereas complete loss of function was found when both mutants were coinjected. These results essentially recapitulate the clinical profiles of the family members, showing a typical dominant negative effect when G196D is coinjected with either AQP2-wt or D150E but not between AQP2-wt and D150E mutant.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
1522-1466
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| pubmed:author |
pubmed-author:ArthusMarie-FrançoiseMF,
pubmed-author:BichetDaniel GDG,
pubmed-author:BissonnettePierreP,
pubmed-author:GuyonCécileC,
pubmed-author:LapointeJean-YvesJY,
pubmed-author:Leduc-NadeauAlexandreA,
pubmed-author:LonerganMichèleM,
pubmed-author:LussierYoannY,
pubmed-author:PerezRafael BedoyaRB,
pubmed-author:TiulpakovAnatolyA
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
297
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
F489-98
|
| pubmed:dateRevised |
2011-4-28
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| pubmed:meshHeading |
pubmed-meshheading:19458121-Amino Acid Sequence,
pubmed-meshheading:19458121-Animals,
pubmed-meshheading:19458121-Aquaporin 2,
pubmed-meshheading:19458121-Cell Line,
pubmed-meshheading:19458121-Cell Membrane,
pubmed-meshheading:19458121-Cell Membrane Permeability,
pubmed-meshheading:19458121-Cell Size,
pubmed-meshheading:19458121-Diabetes Insipidus, Nephrogenic,
pubmed-meshheading:19458121-Female,
pubmed-meshheading:19458121-Genetic Predisposition to Disease,
pubmed-meshheading:19458121-Heterozygote,
pubmed-meshheading:19458121-Homozygote,
pubmed-meshheading:19458121-Humans,
pubmed-meshheading:19458121-Male,
pubmed-meshheading:19458121-Models, Molecular,
pubmed-meshheading:19458121-Molecular Sequence Data,
pubmed-meshheading:19458121-Mutation,
pubmed-meshheading:19458121-Oocytes,
pubmed-meshheading:19458121-Pedigree,
pubmed-meshheading:19458121-Phenotype,
pubmed-meshheading:19458121-Protein Conformation,
pubmed-meshheading:19458121-Protein Transport,
pubmed-meshheading:19458121-Severity of Illness Index,
pubmed-meshheading:19458121-Structure-Activity Relationship,
pubmed-meshheading:19458121-Transfection,
pubmed-meshheading:19458121-Water,
pubmed-meshheading:19458121-Xenopus laevis
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Characterization of D150E and G196D aquaporin-2 mutations responsible for nephrogenic diabetes insipidus: importance of a mild phenotype.
|
| pubmed:affiliation |
Groupe d'Etude des Protéines Membranaires, Département de Physiologie, Université de Montréal, Montréal, Québec, Canada.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|