Regulation of GABAA receptors by fragile X mental retardation protein

International Journal of Physiology, Pathophysiology and Pharmacology

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

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 】

Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABA_A receptors (GABA_ARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on GABA_ARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABA_ARs and phosphatase PTEN, and recorded GABA_AR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs causes increased protein expression of GABA_ARs in cortical neurons, but GABA_AR-mediated whole-cell currents are not potentiated by FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABA_AR activity may play a role in inhibiting GABA_AR function in FMRP-transfected neurons. We further show that FMRP transfection results in an enhanced protein expression of PTEN, which contributes to the inhibition of GABA_AR function in FMRP-transfected neurons. These results indicate that GABA_ARs are regulated by FMRP through both an up-regulation of GABA_AR expression and a PTEN enhancement-induced inhibition of GABA_AR function, suggesting that an abnormal regulation of GABA_AR and PTEN by the loss of FMRP underlies the pathogenesis of FXS.

【 授权许可】

Unknown