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Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4
Several Ca(2+)-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca(2+)-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, t...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867956/ https://www.ncbi.nlm.nih.gov/pubmed/20485495 http://dx.doi.org/10.1371/journal.pone.0010580 |
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author | Strotmann, Rainer Semtner, Marcus Kepura, Frauke Plant, Tim D. Schöneberg, Torsten |
author_facet | Strotmann, Rainer Semtner, Marcus Kepura, Frauke Plant, Tim D. Schöneberg, Torsten |
author_sort | Strotmann, Rainer |
collection | PubMed |
description | Several Ca(2+)-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca(2+)-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca(2+)-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca(2+), displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca(2+)-permeable channels. |
format | Text |
id | pubmed-2867956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28679562010-05-19 Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 Strotmann, Rainer Semtner, Marcus Kepura, Frauke Plant, Tim D. Schöneberg, Torsten PLoS One Research Article Several Ca(2+)-permeable channels, including the non-selective cation channel TRPV4, are subject to Ca(2+)-dependent facilitation. Although it has been clearly demonstrated in functional experiments that calmodulin (CaM) binding to intracellular domains of TRP channels is involved in this process, the molecular mechanism remains elusive. In this study, we provide experimental evidence for a comprehensive molecular model that explains Ca(2+)-dependent facilitation of TRPV4. In the resting state, an intracellular domain from the channel N terminus forms an autoinhibitory complex with a C-terminal domain that includes a high-affinity CaM binding site. CaM binding, secondary to rises in intracellular Ca(2+), displaces the N-terminal domain which may then form a homologous interaction with an identical domain from a second subunit. This represents a novel potentiation mechanism that may also be relevant in other Ca(2+)-permeable channels. Public Library of Science 2010-05-11 /pmc/articles/PMC2867956/ /pubmed/20485495 http://dx.doi.org/10.1371/journal.pone.0010580 Text en Strotmann et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Strotmann, Rainer Semtner, Marcus Kepura, Frauke Plant, Tim D. Schöneberg, Torsten Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title | Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title_full | Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title_fullStr | Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title_full_unstemmed | Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title_short | Interdomain Interactions Control Ca(2+)-Dependent Potentiation in the Cation Channel TRPV4 |
title_sort | interdomain interactions control ca(2+)-dependent potentiation in the cation channel trpv4 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2867956/ https://www.ncbi.nlm.nih.gov/pubmed/20485495 http://dx.doi.org/10.1371/journal.pone.0010580 |
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