Linked Life Data

17715129

Source:http://linkedlifedata.com/resource/pubmed/id/17715129

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2007-10-15
pubmed:databankReference
pubmed:abstractText
The neuronal K-Cl cotransporter KCC2 maintains the low intracellular chloride concentration required for the hyperpolarizing actions of inhibitory neurotransmitters gamma-aminobutyric acid and glycine in the central nervous system. This study shows that the mammalian KCC2 gene (alias Slc12a5) generates two neuron-specific isoforms by using alternative promoters and first exons. The novel KCC2a isoform differs from the only previously known KCC2 isoform (now termed KCC2b) by 40 unique N-terminal amino acid residues, including a putative Ste20-related proline alanine-rich kinase-binding site. Ribonuclease protection and quantitative PCR assays indicated that KCC2a contributes 20-50% of total KCC2 mRNA expression in the neonatal mouse brain stem and spinal cord. In contrast to the marked increase in KCC2b mRNA levels in the cortex during postnatal development, the overall expression of KCC2a remains relatively constant and makes up only 5-10% of total KCC2 mRNA in the mature cortex. A rubidium uptake assay in human embryonic kidney 293 cells showed that the KCC2a isoform mediates furosemide-sensitive ion transport activity comparable with that of KCC2b. Mice that lack both KCC2 isoforms die at birth due to severe motor defects, including disrupted respiratory rhythm, whereas mice with a targeted disruption of the first exon of KCC2b survive for up to 2 weeks but eventually die due to spontaneous seizures. We show that these mice lack KCC2b but retain KCC2a mRNA. Thus, distinct populations of neurons show a differential dependence on the expression of the two isoforms: KCC2a expression in the absence of KCC2b is presumably sufficient to support vital neuronal functions in the brain stem and spinal cord but not in the cortex.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
30570-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:17715129-Animals, pubmed-meshheading:17715129-Base Sequence, pubmed-meshheading:17715129-Binding Sites, pubmed-meshheading:17715129-Brain Stem, pubmed-meshheading:17715129-Cerebral Cortex, pubmed-meshheading:17715129-Furosemide, pubmed-meshheading:17715129-Gene Expression Regulation, pubmed-meshheading:17715129-Humans, pubmed-meshheading:17715129-Ion Transport, pubmed-meshheading:17715129-Mice, pubmed-meshheading:17715129-Mice, Knockout, pubmed-meshheading:17715129-Molecular Sequence Data, pubmed-meshheading:17715129-Nerve Tissue Proteins, pubmed-meshheading:17715129-Promoter Regions, Genetic, pubmed-meshheading:17715129-Protein Isoforms, pubmed-meshheading:17715129-Respiration, pubmed-meshheading:17715129-Rubidium, pubmed-meshheading:17715129-Seizures, pubmed-meshheading:17715129-Sodium Potassium Chloride Symporter Inhibitors, pubmed-meshheading:17715129-Spinal Cord, pubmed-meshheading:17715129-Symporters
pubmed:year
2007
pubmed:articleTitle
A novel N-terminal isoform of the neuron-specific K-Cl cotransporter KCC2.
pubmed:affiliation
Neuroscience Center, Viikinkaari 4, University of Helsinki, Finland. pavel.uvarov@helsinki.fi
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't