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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
1998-6-25
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pubmed:abstractText |
The gap junction protein connexin-43 is normally located at the intercalated discs of cardiac myocytes, and it plays a critical role in the synchronization of their contraction. The mechanism by which connexin-43 is localized within cardiac myocytes is unknown. However, localization of connexin-43 likely involves an interaction with the cytoskeleton; immunofluorescence microscopy showed that in cardiac myocytes, connexin-43 specifically colocalizes with the cytoskeletal proteins ZO-1 and alpha-spectrin. In transfected HEK293 cells, immunoprecipitation experiments using coexpressed epitope-tagged connexin-43 and ZO-1 indicated that ZO-1 links connexin-43 with alpha-spectrin. The domains responsible for the protein-protein interaction between connexin-43 and ZO-1 were identified using affinity binding assays with deleted ZO-1 and connexin-43 fusion proteins. Immunoblot analysis of associated proteins showed that the C-terminal domain of connexin-43 binds to the N-terminal domain of ZO-1. The role of this linkage in gap junction formation was examined by a dominant-negative assay using the N-terminal domain of ZO-1. Overexpression of the N-terminal domain of ZO-1 in connexin-43-expressing cells resulted in redistribution of connexin-43 from cell-cell interfaces to cytoplasmic structures; this intracellular redistribution of connexin-43 coincided with a loss of electrical coupling. We therefore conclude that the linkage between connexin-43 and alpha-spectrin, via ZO-1, may serve to localize connexin-43 at the intercalated discs, thereby generating functional gap junctions in cardiac myocytes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Connexin 43,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Spectrin,
http://linkedlifedata.com/resource/pubmed/chemical/zonula occludens-1 protein
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
22
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12725-31
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9582296-Amino Acid Sequence,
pubmed-meshheading:9582296-Animals,
pubmed-meshheading:9582296-Cell Line,
pubmed-meshheading:9582296-Connexin 43,
pubmed-meshheading:9582296-DNA, Complementary,
pubmed-meshheading:9582296-Humans,
pubmed-meshheading:9582296-Membrane Proteins,
pubmed-meshheading:9582296-Mutagenesis,
pubmed-meshheading:9582296-Myocardium,
pubmed-meshheading:9582296-Phosphoproteins,
pubmed-meshheading:9582296-Rats,
pubmed-meshheading:9582296-Rats, Wistar,
pubmed-meshheading:9582296-Spectrin
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pubmed:year |
1998
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pubmed:articleTitle |
Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes.
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pubmed:affiliation |
Department of Medicine and Pathophysiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan. toyofuku@mr-path.med.osaka-u.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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