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Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes
Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as wel...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Society for Neurochemistry
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695581/ https://www.ncbi.nlm.nih.gov/pubmed/19570022 http://dx.doi.org/10.1042/AN20090001 |
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author | Suadicani, Sylvia O Iglesias, Rodolfo Spray, David C Scemes, Eliana |
author_facet | Suadicani, Sylvia O Iglesias, Rodolfo Spray, David C Scemes, Eliana |
author_sort | Suadicani, Sylvia O |
collection | PubMed |
description | Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X(7)R (P2X(7) receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X(7)R–Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X(7)R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X(7)R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X(7)R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X(7)R stimulation and in the transmission of calcium signals among astrocytes. |
format | Text |
id | pubmed-2695581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | American Society for Neurochemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-26955812009-06-23 Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes Suadicani, Sylvia O Iglesias, Rodolfo Spray, David C Scemes, Eliana ASN Neuro Research Article Purinergic P2 receptors and gap junctions are two groups of proteins involved in the transmission of ICWs (intercellular calcium waves) between astrocytes. The extent to which ICWs spread among these glial cells depends on the amount of ATP released, which can occur through membrane channels, as well as other pathways. Our previous studies have shown that the pore-forming P2X(7)R (P2X(7) receptor) contributes to the amplification of ICW spread by providing sites of ATP release through Panx1 (Pannexin1) channels. To gain insight into the signal transduction events mediating this response we compared the properties of the P2X(7)R–Panx1 complex in astrocytes from a mouse strain (C57Bl/6) containing a naturally occurring point mutation (P451L) in the C-terminus of the P2X(7)R to that of non-mutated receptors (Balb/C mice). Electrophysiological, biochemical, pharmacological and fluorescence imaging techniques revealed that the P451L mutation located in the SH3 domain (a Src tyrosine kinase-binding site) of the C-terminus of the P2X(7)R attenuates Panx1 currents, ATP release and the distance of ICW spread between astrocytes. Similar results were obtained when using the Src tyrosine inhibitor (PP2) and a membrane-permeant peptide spanning the P451L mutation of the P2X(7)R of the C57Bl6 astrocytes. These results support the participation of a tyrosine kinase of the Src family in the initial steps mediating the opening of Panx1 channels following P2X(7)R stimulation and in the transmission of calcium signals among astrocytes. American Society for Neurochemistry 2009-04-14 /pmc/articles/PMC2695581/ /pubmed/19570022 http://dx.doi.org/10.1042/AN20090001 Text en © 2009 The Author(s). http://creativecommons.org/licenses/by-nc/2.5/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Licence (http://creativecommons.org/licenses/by-nc/2.5/) which permits unrestricted non-commerical use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Suadicani, Sylvia O Iglesias, Rodolfo Spray, David C Scemes, Eliana Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title | Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title_full | Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title_fullStr | Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title_full_unstemmed | Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title_short | Point mutation in the mouse P2X(7) receptor affects intercellular calcium waves in astrocytes |
title_sort | point mutation in the mouse p2x(7) receptor affects intercellular calcium waves in astrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2695581/ https://www.ncbi.nlm.nih.gov/pubmed/19570022 http://dx.doi.org/10.1042/AN20090001 |
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