Linked Life Data

20403973

Source:http://linkedlifedata.com/resource/pubmed/id/20403973

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 12
pubmed:dateCreated
2010-6-16
pubmed:abstractText
Aquaporin-2 (AQP2), located at the luminal side of the collecting duct principal cells, is a water channel responsible for the final concentration of urine. Lack of function, often occurring through mistargeting of mutated proteins, induces nephrogenic diabetes insipidus (NDI), a condition characterized by large urinary volumes. In the present study, two new mutations (K228E and V24A) identified in NDI-affected individuals from distinct families along with the already reported R187C were analysed in comparison to the wild-type protein (AQP2-wt) using Xenopus laevis oocytes and a mouse collecting duct cell-line (mIMCD-3). Initial data in oocytes showed that all mutations were adequately expressed at reduced levels when compared to AQP2-wt. K228E and V24A were found to be properly targeted at the plasma membrane and exhibited adequate functionality similar to AQP2-wt, as opposed to R187C which was retained in internal stores and was thus inactive. In coexpression studies using oocytes, R187C impeded the functionality of all other AQP2 variants while combinations with K228E, V24A and AQP2-wt only showed additive functionalities. When expressed in mIMCD-3 cells, forskolin treatment efficiently promoted the targeting of AQP2-wt at the plasma membrane (>90%) while K228E only weakly responded to the same treatment (approximately 20%) and both V24A and R187C remained completely insensitive to the treatment. We concluded that both V24A and K228E are intrinsically functional water channels that lack a proper response to vasopressin, which leads to NDI as found in both compound mutations studied (K228E + R187C and V24A + R187C). The discrepancies in plasma membrane targeting response found in both expression systems stress the need to evaluate such data using mammalian cell systems.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-10228154, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-10411689, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-10523405, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-10997928, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11001488, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11274397, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11297561, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11374071, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11401515, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11536078, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-11929850, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-12050236, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-12191971, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-14593099, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-14662748, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-16120822, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-16288724, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-16825342, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-17079335, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-19458121, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-19574955, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-7537761, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-9593782, http://linkedlifedata.com/resource/pubmed/commentcorrection/20403973-9649557
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1469-7793
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
588
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2205-18
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:20403973-Adult, pubmed-meshheading:20403973-Amino Acid Sequence, pubmed-meshheading:20403973-Animals, pubmed-meshheading:20403973-Aquaporin 2, pubmed-meshheading:20403973-Cell Line, pubmed-meshheading:20403973-Cell Membrane, pubmed-meshheading:20403973-Diabetes Insipidus, Nephrogenic, pubmed-meshheading:20403973-Female, pubmed-meshheading:20403973-Forskolin, pubmed-meshheading:20403973-Genes, Recessive, pubmed-meshheading:20403973-Genetic Predisposition to Disease, pubmed-meshheading:20403973-Humans, pubmed-meshheading:20403973-Kidney Tubules, Collecting, pubmed-meshheading:20403973-Male, pubmed-meshheading:20403973-Mice, pubmed-meshheading:20403973-Molecular Sequence Data, pubmed-meshheading:20403973-Mutation, pubmed-meshheading:20403973-Oocytes, pubmed-meshheading:20403973-Pedigree, pubmed-meshheading:20403973-Protein Transport, pubmed-meshheading:20403973-Transfection, pubmed-meshheading:20403973-Vasopressins, pubmed-meshheading:20403973-Water, pubmed-meshheading:20403973-Xenopus laevis
pubmed:year
2010
pubmed:articleTitle
New autosomal recessive mutations in aquaporin-2 causing nephrogenic diabetes insipidus through deficient targeting display normal expression in Xenopus oocytes.
pubmed:affiliation
Groupe d' Etude des Protéines Membranaires (GEPROM), département de Physiologie, Université de Montréal, Montréal, Québec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't