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Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate
Cell–cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein–coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell–cell communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosp...
Autores principales: | , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064287/ https://www.ncbi.nlm.nih.gov/pubmed/17535964 http://dx.doi.org/10.1083/jcb.200610144 |
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author | van Zeijl, Leonie Ponsioen, Bas Giepmans, Ben N.G. Ariaens, Aafke Postma, Friso R. Várnai, Péter Balla, Tamas Divecha, Nullin Jalink, Kees Moolenaar, Wouter H. |
author_facet | van Zeijl, Leonie Ponsioen, Bas Giepmans, Ben N.G. Ariaens, Aafke Postma, Friso R. Várnai, Péter Balla, Tamas Divecha, Nullin Jalink, Kees Moolenaar, Wouter H. |
author_sort | van Zeijl, Leonie |
collection | PubMed |
description | Cell–cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein–coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell–cell communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P(2)) from the plasma membrane. Knockdown of phospholipase Cβ3 (PLCβ3) inhibits PtdIns(4,5)P(2) hydrolysis and keeps Cx43 channels open after receptor activation. Using a translocatable 5-phosphatase, we show that PtdIns(4,5)P(2) depletion is sufficient to close Cx43 channels. When PtdIns(4,5)P(2) is overproduced by PtdIns(4)P 5-kinase, Cx43 channel closure is impaired. We find that the Cx43 binding partner zona occludens 1 (ZO-1) interacts with PLCβ3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5)P(2)-hydrolyzing receptors to inhibit cell–cell communication, but not for receptor–PLC coupling. Our results show that PtdIns(4,5)P(2) is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLCβ3 and Cx43 into a signaling complex to allow regulation of cell–cell communication by localized changes in PtdIns(4,5)P(2). |
format | Text |
id | pubmed-2064287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20642872007-12-04 Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate van Zeijl, Leonie Ponsioen, Bas Giepmans, Ben N.G. Ariaens, Aafke Postma, Friso R. Várnai, Péter Balla, Tamas Divecha, Nullin Jalink, Kees Moolenaar, Wouter H. J Cell Biol Research Articles Cell–cell communication through connexin43 (Cx43)-based gap junction channels is rapidly inhibited upon activation of various G protein–coupled receptors; however, the mechanism is unknown. We show that Cx43-based cell–cell communication is inhibited by depletion of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P(2)) from the plasma membrane. Knockdown of phospholipase Cβ3 (PLCβ3) inhibits PtdIns(4,5)P(2) hydrolysis and keeps Cx43 channels open after receptor activation. Using a translocatable 5-phosphatase, we show that PtdIns(4,5)P(2) depletion is sufficient to close Cx43 channels. When PtdIns(4,5)P(2) is overproduced by PtdIns(4)P 5-kinase, Cx43 channel closure is impaired. We find that the Cx43 binding partner zona occludens 1 (ZO-1) interacts with PLCβ3 via its third PDZ domain. ZO-1 is essential for PtdIns(4,5)P(2)-hydrolyzing receptors to inhibit cell–cell communication, but not for receptor–PLC coupling. Our results show that PtdIns(4,5)P(2) is a key regulator of Cx43 channel function, with no role for other second messengers, and suggest that ZO-1 assembles PLCβ3 and Cx43 into a signaling complex to allow regulation of cell–cell communication by localized changes in PtdIns(4,5)P(2). The Rockefeller University Press 2007-06-04 /pmc/articles/PMC2064287/ /pubmed/17535964 http://dx.doi.org/10.1083/jcb.200610144 Text en Copyright © 2007, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles van Zeijl, Leonie Ponsioen, Bas Giepmans, Ben N.G. Ariaens, Aafke Postma, Friso R. Várnai, Péter Balla, Tamas Divecha, Nullin Jalink, Kees Moolenaar, Wouter H. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title | Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title_full | Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title_fullStr | Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title_full_unstemmed | Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title_short | Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
title_sort | regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064287/ https://www.ncbi.nlm.nih.gov/pubmed/17535964 http://dx.doi.org/10.1083/jcb.200610144 |
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