Source:http://linkedlifedata.com/resource/pubmed/id/15123711
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
28
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| pubmed:dateCreated |
2004-7-5
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| pubmed:abstractText |
TRPV5 and TRPV6 are members of the superfamily of transient receptor potential (TRP) channels and facilitate Ca(2+) influx in a variety of epithelial cells. The activity of these Ca(2+) channels is tightly controlled by the intracellular Ca(2+) concentration in close vicinity to the channel mouth. The molecular mechanism underlying the Ca(2+)-dependent activity of TRPV5/TRPV6 is, however, still unknown. Here, the putative role of calmodulin (CaM) as the Ca(2+) sensor mediating the regulation of channel activity was investigated. Overexpression of Ca(2+)-insensitive CaM mutants (CaM(1234) and CaM(34)) significantly reduced the Ca(2+) as well as the Na(+) current of TRPV6- but not that of TRPV5-expressing HEK293 cells. By combining pull-down assays and co-immunoprecipitations, we demonstrated that CaM binds to both TRPV5 and TRPV6 in a Ca(2+)-dependent fashion. The binding of CaM to TRPV6 was localized to the transmembrane domain (TRPV6(327-577)) and consensus CaM-binding motifs located in the N (1-5-10 motif, TRPV6(88-97)) and C termini (1-8-14 motif, TRPV6(643-656)), suggesting a mechanism of regulation involving multiple interaction sites. Subsequently, chimeric TRPV6/TRPV5 proteins, in which the N and/or C termini of TRPV6 were substituted by that of TRPV5, were co-expressed with CaM(34) in HEK293 cells. Exchanging, the N and/or the C termini of TRPV6 by that of TRPV5 did not affect the CaM(34)-induced reduction of the Ca(2+) and Na(+) currents. These results suggest that CaM positively affects TRPV6 activity upon Ca(2+) binding to EF-hands 3 and 4, located in the high Ca(2+) affinity CaM C terminus, which involves the N and C termini and the transmembrane domain of TRPV6.
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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/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TRPV Cation Channels,
http://linkedlifedata.com/resource/pubmed/chemical/TRPV6 channel
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Jul
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
9
|
| pubmed:volume |
279
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
28855-61
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15123711-Amino Acid Sequence,
pubmed-meshheading:15123711-Animals,
pubmed-meshheading:15123711-Binding Sites,
pubmed-meshheading:15123711-Calcium,
pubmed-meshheading:15123711-Calcium Channels,
pubmed-meshheading:15123711-Calmodulin,
pubmed-meshheading:15123711-Cell Line,
pubmed-meshheading:15123711-Epithelial Cells,
pubmed-meshheading:15123711-Humans,
pubmed-meshheading:15123711-Mice,
pubmed-meshheading:15123711-Molecular Sequence Data,
pubmed-meshheading:15123711-Oocytes,
pubmed-meshheading:15123711-Patch-Clamp Techniques,
pubmed-meshheading:15123711-Protein Binding,
pubmed-meshheading:15123711-Rabbits,
pubmed-meshheading:15123711-Recombinant Fusion Proteins,
pubmed-meshheading:15123711-Sequence Alignment,
pubmed-meshheading:15123711-TRPV Cation Channels,
pubmed-meshheading:15123711-Xenopus
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| pubmed:year |
2004
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| pubmed:articleTitle |
Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin.
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| pubmed:affiliation |
Department of Physiology, Nijmegen Center for Molecular Life Sciences, University Medical Centre Nijmegen, NL-6500 HB Nijmegen, The Netherlands.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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