Regulation of GABAA receptors by fragile X mental retardation protein

International Journal of Physiology, Pathophysiology and Pharmacology

Juan Chen¹  Zefen Wang¹  Qi Wan¹  Baosong Liu¹  Lijun Li¹  Zhiqiang Li¹ 

[1] Toronto Western Research Institute, University of Toronto, Toronto, Ontario, Canada, M5T 2S8; Department of Physiology, School of Medicine, Wuhan University, 185 Donghu Road, Wuhan 430071, China; University of Nevada School of Medicine, 1664 North Virginia Street, MS0352, Reno, NV 89557. These authors contributed equally to this work.

关键词: Fragile X syndrome;    fragile X mental retardation protein;    GABAA receptor;    PTEN;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

FragileXsyndrome(FXS)iscausedbythelossoffragileXmentalretardationprotein(FMRP).ThedeficiencyofGABAAreceptors(GABAARs)isimplicatedinFXS.However,theunderlyingmechanismsremainunclear.ToinvestigatetheeffectofFMRPonGABAARs,wetransfectedFMRPcDNAsinratcorticalneurons.WemeasuredtheproteinexpressionofGABAARsandphosphatasePTEN,andrecordedGABAAR-mediatedwhole-cellcurrentsinthetransfectedneurons.WeshowthatthetransfectionofFMRPcDNAscausesincreasedproteinexpressionofGABAARsincorticalneurons,butGABAAR-mediatedwhole-cellcurrentsarenotpotentiatedbyFMRPtransfection.TheseresultssuggestthepossibilitythatintracellularsignalingantagonizingGABAARactivitymayplayaroleininhibitingGABAARfunctioninFMRP-transfectedneurons.WefurthershowthatFMRPtransfectionresultsinanenhancedproteinexpressionofPTEN,whichcontributestotheinhibitionofGABAARfunctioninFMRP-transfectedneurons.TheseresultsindicatethatGABAARsareregulatedbyFMRPthroughbothanup-regulationofGABAARexpressionandaPTENenhancement-inducedinhibitionofGABAARfunction,suggestingthatanabnormalregulationofGABAARandPTENbythelossofFMRPunderliesthepathogenesisofFXS.(IJPPP1307006).

【 授权许可】

Unknown