Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
1998-9-14
pubmed:abstractText
The NHE3 isoform of the Na+/H+ exchanger localizes to both the plasmalemmal and endosomal compartments in polarized epithelial and transfected Chinese hamster ovary (AP-1) cells. It is unclear how the distribution of NHE3 between these compartments is regulated. In this study, we examined the potential involvement of phosphatidylinositol 3'-kinase (PI3-K) in regulating the activity and distribution of NHE3, as this lipid kinase has been implicated in modulating vesicular traffic in the endosomal recycling pathway. Wortmannin and LY294002, both potent inhibitors of PI3-K, markedly inhibited NHE3-mediated H+ extrusion across the plasma membrane in a concentration- and time-dependent manner. The subcellular distribution of the antiporters was monitored by transfecting epitope-tagged NHE3 into AP-1 cells. In parallel with the inhibition of transport, PI3-K antagonists induced a pronounced loss of NHE3 from the cell surface and its accumulation in an intracellular compartment, as assessed by immunofluorescence microscopy and enzyme-linked immunosorbent assays. Further analysis using cells transfected with antiporters bearing an external epitope tag revealed that the redistribution reflected primarily a decrease in the rate of recycling of intracellular NHE3 to the cell surface. The wortmannin-induced inhibition and redistribution of NHE3 were prevented when cells were incubated at 4 degreesC, consistent with the known temperature dependence of the endocytic process. These observations demonstrate that NHE3 activity is controlled by dynamic endocytic and recycling events that are modulated by PI3-K.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
14
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20828-36
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9694828-Amino Acid Sequence, pubmed-meshheading:9694828-Androstadienes, pubmed-meshheading:9694828-Animals, pubmed-meshheading:9694828-CHO Cells, pubmed-meshheading:9694828-Chromones, pubmed-meshheading:9694828-Cricetinae, pubmed-meshheading:9694828-Endocytosis, pubmed-meshheading:9694828-Endosomes, pubmed-meshheading:9694828-Enzyme Inhibitors, pubmed-meshheading:9694828-Epitopes, pubmed-meshheading:9694828-Exocytosis, pubmed-meshheading:9694828-Kinetics, pubmed-meshheading:9694828-Molecular Sequence Data, pubmed-meshheading:9694828-Morpholines, pubmed-meshheading:9694828-Phosphatidylinositol 3-Kinases, pubmed-meshheading:9694828-Rats, pubmed-meshheading:9694828-Sodium-Hydrogen Antiporter, pubmed-meshheading:9694828-Subcellular Fractions, pubmed-meshheading:9694828-Temperature
pubmed:year
1998
pubmed:articleTitle
Endosomal recycling of the Na+/H+ exchanger NHE3 isoform is regulated by the phosphatidylinositol 3-kinase pathway.
pubmed:affiliation
Cell Biology Programme, Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't