Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-6-5
pubmed:abstractText
The PDZ-binding protein PDZK1 (CAP70/PDZ-dc-1/NHERF3) in vitro binds to cystic fibrosis transmembrane conductance regulator (CFTR), the anion exchangers SLC26A3 and SLC26A6 and the Na(+)/H(+) exchanger NHE3, all of which are major transport proteins for intestinal anion secretion and salt absorption. This study was undertaken to search for a role of PDZK1 in regulating electrolyte transport in native murine small intestine. Short circuit current (I (SC)) and HCO-(3) secretory rate (J(HCO-)(3)) were measured to assess electrogenic anion secretion; (22)Na(+) fluxes to assess sodium absorption in isolated small intestine. NHE3, CFTR, as well as NHERF1, NHERF2, and PDZK1 messenger RNA (mRNA) expression levels, and NHE3 total enterocyte and brush border membrane (BBM) protein abundance were determined by quantitative polymerase chain reaction (PCR) and Western analysis. NHE3 localization was performed by immunohistochemistry. In pdzk1 -/- jejunal mucosa, basal net Na(+) absorption as well as the inhibition of Na(+) absorption by forskolin was significantly reduced. In pdzk1 -/- duodenal mucosa, identical basal I (SC) and (J(HCO-)(3)) but a significant, yet mild, reduction of forskolin-stimulated Delta(J(HCO-)(3)) and DeltaI (SC) was observed compared to +/+ tissue. Tissue conductance, morphological features, and the DeltaI (SC) and increase in (22)Na(+) absorption in response to luminal glucose was identical in pdzk1 +/+ and -/- small intestine, ruling out a general absorptive defect. While CFTR mRNA expression levels were unchanged, NHE3 mRNA expression levels were significantly increased in small intestinal mucosa of pdzk1 -/- mice. Total enterocyte and BBM abundance was not significantly different, suggesting an increased NHE3 turnover, possibly due to reduced NHE3 membrane retention time. Lack of the PDZ-adapter protein PDZK1 in murine small intestine causes a mild reduction in maximal CFTR activation, but a severe defect in electroneutral Na(+) absorption.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bicarbonates, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP, http://linkedlifedata.com/resource/pubmed/chemical/Cystic Fibrosis Transmembrane..., http://linkedlifedata.com/resource/pubmed/chemical/Forskolin, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/PDZK1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Sodium, http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter, http://linkedlifedata.com/resource/pubmed/chemical/sodium-hydrogen exchanger 3, http://linkedlifedata.com/resource/pubmed/chemical/sodium-hydrogen exchanger...
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0031-6768
pubmed:author
pubmed:issnType
Print
pubmed:volume
454
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-86
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed-meshheading:17347851-Animals, pubmed-meshheading:17347851-Bicarbonates, pubmed-meshheading:17347851-Cyclic AMP, pubmed-meshheading:17347851-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:17347851-Down-Regulation, pubmed-meshheading:17347851-Forskolin, pubmed-meshheading:17347851-Gene Expression Regulation, pubmed-meshheading:17347851-Intestinal Absorption, pubmed-meshheading:17347851-Intestine, Small, pubmed-meshheading:17347851-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:17347851-Ion Transport, pubmed-meshheading:17347851-Mice, pubmed-meshheading:17347851-Mice, Knockout, pubmed-meshheading:17347851-Phosphoproteins, pubmed-meshheading:17347851-RNA, Messenger, pubmed-meshheading:17347851-Sodium, pubmed-meshheading:17347851-Sodium-Hydrogen Antiporter
pubmed:year
2007
pubmed:articleTitle
Down regulation of small intestinal ion transport in PDZK1- (CAP70/NHERF3) deficient mice.
pubmed:affiliation
Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't