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The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes

In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, re...

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Autores principales: Abudara, Verónica, Bechberger, John, Freitas-Andrade, Moises, De Bock, Marijke, Wang, Nan, Bultynck, Geert, Naus, Christian C., Leybaert, Luc, Giaume, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204617/
https://www.ncbi.nlm.nih.gov/pubmed/25374505
http://dx.doi.org/10.3389/fncel.2014.00306
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author Abudara, Verónica
Bechberger, John
Freitas-Andrade, Moises
De Bock, Marijke
Wang, Nan
Bultynck, Geert
Naus, Christian C.
Leybaert, Luc
Giaume, Christian
author_facet Abudara, Verónica
Bechberger, John
Freitas-Andrade, Moises
De Bock, Marijke
Wang, Nan
Bultynck, Geert
Naus, Christian C.
Leybaert, Luc
Giaume, Christian
author_sort Abudara, Verónica
collection PubMed
description In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively. Both types of Cx channels are permeable to ions and small signaling molecules allowing astrocytes to establish dynamic interactions with neurons. So far, most pharmacological approaches currently available do not distinguish between these two channel functions, stressing the need to develop new specific molecular tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now evidence indicating that at least Cx43 operates as a gap junction channel as well as a hemichannel in these cells. Based on studies in primary cultures as well as in acute hippocampal slices, we report here that Gap19, a nonapeptide derived from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels. This peptide, which not only selectively inhibits hemichannels but is also specific for Cx43, can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the brain parenchyma. As a result, Gap19 combined with other tools opens up new avenues to decipher the role of Cx43 hemichannels in interactions between astrocytes and neurons in physiological as well as pathological situations.
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spelling pubmed-42046172014-11-05 The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes Abudara, Verónica Bechberger, John Freitas-Andrade, Moises De Bock, Marijke Wang, Nan Bultynck, Geert Naus, Christian C. Leybaert, Luc Giaume, Christian Front Cell Neurosci Neuroscience In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively. Both types of Cx channels are permeable to ions and small signaling molecules allowing astrocytes to establish dynamic interactions with neurons. So far, most pharmacological approaches currently available do not distinguish between these two channel functions, stressing the need to develop new specific molecular tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now evidence indicating that at least Cx43 operates as a gap junction channel as well as a hemichannel in these cells. Based on studies in primary cultures as well as in acute hippocampal slices, we report here that Gap19, a nonapeptide derived from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels. This peptide, which not only selectively inhibits hemichannels but is also specific for Cx43, can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the brain parenchyma. As a result, Gap19 combined with other tools opens up new avenues to decipher the role of Cx43 hemichannels in interactions between astrocytes and neurons in physiological as well as pathological situations. Frontiers Media S.A. 2014-10-21 /pmc/articles/PMC4204617/ /pubmed/25374505 http://dx.doi.org/10.3389/fncel.2014.00306 Text en Copyright © 2014 Abudara, Bechberger, Freitas-Andrade, De Bock, Wang, Bultynck, Naus, Leybaert and Giaume. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Abudara, Verónica
Bechberger, John
Freitas-Andrade, Moises
De Bock, Marijke
Wang, Nan
Bultynck, Geert
Naus, Christian C.
Leybaert, Luc
Giaume, Christian
The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title_full The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title_fullStr The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title_full_unstemmed The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title_short The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
title_sort connexin43 mimetic peptide gap19 inhibits hemichannels without altering gap junctional communication in astrocytes
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4204617/
https://www.ncbi.nlm.nih.gov/pubmed/25374505
http://dx.doi.org/10.3389/fncel.2014.00306
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