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The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment
Sensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here we examine the role of the SH3 domain of postsynaptic density 95 (PSD95) by using mice that carry a single amino-acid substitution in the polyproline-binding site. Testing mul...
| Autores principales: | , , , , , , , , , , , , , |
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| Formato: | Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group
2010
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892321/ https://www.ncbi.nlm.nih.gov/pubmed/20467438 http://dx.doi.org/10.1038/embor.2010.63 |
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| author | Arbuckle, Margaret I Komiyama, Noboru H Delaney, Ada Coba, Marcelo Garry, Emer M Rosie, Roberta Allchorne, Andrew J Forsyth, Lynsey H Bence, Matthew Carlisle, Holly J O'Dell, Thomas J Mitchell, Rory Fleetwood-Walker, Susan M Grant, Seth G N |
| author_facet | Arbuckle, Margaret I Komiyama, Noboru H Delaney, Ada Coba, Marcelo Garry, Emer M Rosie, Roberta Allchorne, Andrew J Forsyth, Lynsey H Bence, Matthew Carlisle, Holly J O'Dell, Thomas J Mitchell, Rory Fleetwood-Walker, Susan M Grant, Seth G N |
| author_sort | Arbuckle, Margaret I |
| collection | PubMed |
| description | Sensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here we examine the role of the SH3 domain of postsynaptic density 95 (PSD95) by using mice that carry a single amino-acid substitution in the polyproline-binding site. Testing multiple forms of plasticity we found sensitization to inflammation was specifically attenuated. The inflammatory response required recruitment of phosphatidylinositol-3-kinase-C2α to the SH3-binding site of PSD95. In wild-type mice, wortmannin or peptide competition attenuated the sensitization. These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain. |
| format | Text |
| id | pubmed-2892321 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2010 |
| publisher | Nature Publishing Group |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-28923212010-06-28 The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment Arbuckle, Margaret I Komiyama, Noboru H Delaney, Ada Coba, Marcelo Garry, Emer M Rosie, Roberta Allchorne, Andrew J Forsyth, Lynsey H Bence, Matthew Carlisle, Holly J O'Dell, Thomas J Mitchell, Rory Fleetwood-Walker, Susan M Grant, Seth G N EMBO Rep Scientific Reports Sensitization to inflammatory pain is a pathological form of neuronal plasticity that is poorly understood and treated. Here we examine the role of the SH3 domain of postsynaptic density 95 (PSD95) by using mice that carry a single amino-acid substitution in the polyproline-binding site. Testing multiple forms of plasticity we found sensitization to inflammation was specifically attenuated. The inflammatory response required recruitment of phosphatidylinositol-3-kinase-C2α to the SH3-binding site of PSD95. In wild-type mice, wortmannin or peptide competition attenuated the sensitization. These results show that different types of behavioural plasticity are mediated by specific domains of PSD95 and suggest novel therapeutic avenues for reducing inflammatory pain. Nature Publishing Group 2010-06 2010-05-14 /pmc/articles/PMC2892321/ /pubmed/20467438 http://dx.doi.org/10.1038/embor.2010.63 Text en Copyright © 2010, European Molecular Biology Organization http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission. |
| spellingShingle | Scientific Reports Arbuckle, Margaret I Komiyama, Noboru H Delaney, Ada Coba, Marcelo Garry, Emer M Rosie, Roberta Allchorne, Andrew J Forsyth, Lynsey H Bence, Matthew Carlisle, Holly J O'Dell, Thomas J Mitchell, Rory Fleetwood-Walker, Susan M Grant, Seth G N The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title | The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title_full | The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title_fullStr | The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title_full_unstemmed | The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title_short | The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| title_sort | sh3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment |
| topic | Scientific Reports |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892321/ https://www.ncbi.nlm.nih.gov/pubmed/20467438 http://dx.doi.org/10.1038/embor.2010.63 |
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