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

被引：21

作者：

Arbuckle, Margaret I. ^{[2
]}

Komiyama, Noboru H. ^{[1
]}

Delaney, Ada ^{[2
]}

Coba, Marcelo ^{[1
]}

Garry, Emer M. ^{[2
]}

Rosie, Roberta ^{[2
]}

Allchorne, Andrew J. ^{[2
]}

Forsyth, Lynsey H. ^{[2
]}

Bence, Matthew ^{[2
]}

Carlisle, Holly J. ^{[3
]}

O'Dell, Thomas J. ^{[3
]}

Mitchell, Rory ^{[2
]}

Fleetwood-Walker, Susan M. ^{[2
]}

Grant, Seth G. N. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Genes Cognit Programme, Cambridge, England

[2] Univ Edinburgh, Ctr Neuroregenerat, Inst Immunol & Infect, Edinburgh EH9 3JT, Midlothian, Scotland

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90024 USA

来源：

EMBO REPORTS | 2010年 / 11卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

nociception; inflammation; PSD95; SH3; domain; CRYSTAL-STRUCTURE; NMDA RECEPTOR; PLASTICITY; COMPLEXES; 3-KINASE; PROTEIN; PSD-95; SENSITIZATION; RESIDUES; GENES;

D O I：

10.1038/embor.2010.63

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：473 / 478

页数：6

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