The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment

M. I. Arbuckle, N. H. Komiyama, A. Delaney, M. Coba, E. M. Garry, R. Rosie, A. J. Allchorne, L. H. Forsyth, M. Bence, H. J. Carlisle, T. J. O'Dell, Rory Mitchell, S. M. Fleetwood-Walker, Seth Grant

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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-C2 alpha 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.
Original languageEnglish
Pages (from-to)473-478
Number of pages6
JournalEMBO Reports
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Dive into the research topics of 'The SH3 domain of postsynaptic density 95 mediates inflammatory pain through phosphatidylinositol-3-kinase recruitment'. Together they form a unique fingerprint.

Cite this