Source:http://linkedlifedata.com/resource/pubmed/id/16260777
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
2006-1-12
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| pubmed:abstractText |
KCNQ2 and KCNQ3 K+ channel subunits underlie the muscarinic-regulated K+ current (I(KM)), a widespread regulator of neuronal excitability. Mutations in KCNQ2- or KCNQ3-encoding genes cause benign familiar neonatal convulsions (BFNCs), a rare autosomal-dominant idiopathic epilepsy of the newborn. In the present study, we have investigated, by means of electrophysiological, biochemical, and immunocytochemical techniques in transiently transfected cells, the consequences prompted by a BFNC-causing 1-bp deletion (2043deltaT) in the KCNQ2 gene; this frameshift mutation caused the substitution of the last 163 amino acids of the KCNQ2 C terminus and the extension of the subunit by additional 56 residues. The 2043deltaT mutation abolished voltage-gated K+ currents produced upon homomeric expression of KCNQ2 subunits, dramatically reduced the steady-state cellular levels of KCNQ2 subunits, and prevented their delivery to the plasma membrane. Metabolic labeling experiments revealed that mutant KCNQ2 subunits underwent faster degradation; 10-h treatment with the proteasomal inhibitor MG132 (20 microm) at least partially reversed such enhanced degradation. Co-expression with KCNQ3 subunits reduced the degradation rate of mutant KCNQ2 subunits and led to their expression on the plasma membrane. Finally, co-expression of KCNQ2 2043deltaT together with KCNQ3 subunits generated functional voltage-gated K+ currents having pharmacological and biophysical properties of heteromeric channels. Collectively, the present results suggest that mutation-induced reduced stability of KCNQ2 subunits may cause epilepsy in neonates.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
|
| pubmed:issn |
0021-9258
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| pubmed:author |
pubmed-author:AnnunziatoLucioL,
pubmed-author:BarreseVincenzoV,
pubmed-author:BelliniGiuliaG,
pubmed-author:BonattiStefanoS,
pubmed-author:CastaldoPasqualinaP,
pubmed-author:IodiceLuisaL,
pubmed-author:MiceliFrancescoF,
pubmed-author:Miraglia del GiudiceEmanueleE,
pubmed-author:PascottoAntonioA,
pubmed-author:SoldovieriMaria VirginiaMV,
pubmed-author:TaglialatelaMaurizioM
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| pubmed:issnType |
Print
|
| pubmed:day |
6
|
| pubmed:volume |
281
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
418-28
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16260777-Animals,
pubmed-meshheading:16260777-CHO Cells,
pubmed-meshheading:16260777-Carcinoma, Hepatocellular,
pubmed-meshheading:16260777-Cell Line, Tumor,
pubmed-meshheading:16260777-Cell Membrane,
pubmed-meshheading:16260777-Cricetinae,
pubmed-meshheading:16260777-Epilepsy, Benign Neonatal,
pubmed-meshheading:16260777-Frameshift Mutation,
pubmed-meshheading:16260777-Green Fluorescent Proteins,
pubmed-meshheading:16260777-Humans,
pubmed-meshheading:16260777-Infant, Newborn,
pubmed-meshheading:16260777-KCNQ2 Potassium Channel,
pubmed-meshheading:16260777-KCNQ3 Potassium Channel,
pubmed-meshheading:16260777-Liver Neoplasms,
pubmed-meshheading:16260777-Mutagenesis,
pubmed-meshheading:16260777-Patch-Clamp Techniques,
pubmed-meshheading:16260777-Protein Subunits,
pubmed-meshheading:16260777-Transfection
|
| pubmed:year |
2006
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| pubmed:articleTitle |
Decreased subunit stability as a novel mechanism for potassium current impairment by a KCNQ2 C terminus mutation causing benign familial neonatal convulsions.
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| pubmed:affiliation |
Division of Pharmacology, Department of Neuroscience, University of Naples Federico II, 80131 Naples.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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