Source:http://linkedlifedata.com/resource/pubmed/id/11929850
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
2002-4-3
|
| pubmed:abstractText |
Autosomal nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by mutations in the Aquaporin-2 (AQP2) gene. Analysis of a new family with dominant NDI revealed a single nucleotide deletion (727deltaG) in one AQP2 allele, which encoded an AQP2 mutant with an altered and extended C-terminal tail. When expressed in oocytes, the tetrameric AQP2-727deltaG was retained within the cell. When co-expressed, AQP2-727deltaG, but not a mutant in recessive NDI (AQP2-R187C), formed hetero-oligomers with wild-type (wt) AQP2 and reduced the water permeability of these oocytes, because of a reduced plasma membrane expression of wt-AQP2. Expressed in renal epithelial cells, AQP2-727deltaG predominantly localized to the basolateral membrane and late endosomes/lysosomes, whereas wt-AQP2 was expressed in the apical membrane. Upon co-expressing in these cells, wt-AQP2 and AQP2-727deltaG mainly co-localized to late endosomes/lysosomes. In conclusion, hetero-oligomerization of AQP2-727deltaG with wt-AQP2 and consequent mistargeting of this complex to late endosomes/lysosomes results in absence of AQP2 in the apical membrane, which can explain dominant NDI in this family. Together with other mutants in dominant NDI, our data reveal that a misrouting, instead of a lack of function, is a general mechanism for the 'loss of function' phenotype in dominant NDI and visualizes for the first time a mislocalization of a wild-type protein to late endosomes/lysosomes in polarized cells after oligomerization with a mutant protein.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0964-6906
|
| pubmed:author |
pubmed-author:ArthusMarie-FrancoiseMF,
pubmed-author:BichetDaniel GDG,
pubmed-author:DeenPeter M TPM,
pubmed-author:JeckNikolaN,
pubmed-author:LonerganMicheleM,
pubmed-author:MarrNannetteN,
pubmed-author:OkscheAlexanderA,
pubmed-author:RosenthalWalterW,
pubmed-author:SeyberthHannsjörg WHW,
pubmed-author:van OsCarel HCH
|
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
11
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
779-89
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:11929850-Amino Acid Sequence,
pubmed-meshheading:11929850-Animals,
pubmed-meshheading:11929850-Aquaporins,
pubmed-meshheading:11929850-Base Sequence,
pubmed-meshheading:11929850-Cell Membrane,
pubmed-meshheading:11929850-Cells, Cultured,
pubmed-meshheading:11929850-Deamino Arginine Vasopressin,
pubmed-meshheading:11929850-Diabetes Insipidus, Nephrogenic,
pubmed-meshheading:11929850-Dogs,
pubmed-meshheading:11929850-Endosomes,
pubmed-meshheading:11929850-Female,
pubmed-meshheading:11929850-Humans,
pubmed-meshheading:11929850-Immunohistochemistry,
pubmed-meshheading:11929850-Kidney,
pubmed-meshheading:11929850-Lysosomes,
pubmed-meshheading:11929850-Male,
pubmed-meshheading:11929850-Molecular Sequence Data,
pubmed-meshheading:11929850-Oocytes,
pubmed-meshheading:11929850-Permeability,
pubmed-meshheading:11929850-Point Mutation,
pubmed-meshheading:11929850-Protein Transport,
pubmed-meshheading:11929850-Renal Agents,
pubmed-meshheading:11929850-Sequence Deletion,
pubmed-meshheading:11929850-Water
|
| pubmed:year |
2002
|
| pubmed:articleTitle |
Heteroligomerization of an Aquaporin-2 mutant with wild-type Aquaporin-2 and their misrouting to late endosomes/lysosomes explains dominant nephrogenic diabetes insipidus.
|
| pubmed:affiliation |
160 Department of Cell Physiology, Nijmegen Center of Molecular Life Sciences, University Medical Center St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|