IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2013;5(3):169-176

Original Article
Regulation of GABAA receptors by fragile X mental retardation protein

Baosong Liu, Lijun Li, Juan Chen, Zefen Wang, Zhiqiang Li, Qi Wan

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.

Received July 18, 2013; Accepted August 2, 2013; Epub September 10, 2013; Published September 15, 2013

Abstract: Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP). The deficiency of GABAA
receptors (GABAARs) is implicated in FXS. However, the underlying mechanisms remain unclear. To investigate the effect of FMRP on
GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured the protein expression of GABAARs and phosphatase
PTEN, and recorded GABAAR-mediated whole-cell currents in the transfected neurons. We show that the transfection of FMRP cDNAs
causes increased protein expression of GABAARs in cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by
FMRP transfection. These results suggest the possibility that intracellular signaling antagonizing GABAAR activity may play a role in
inhibiting GABAAR 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 GABAAR function in FMRP-transfected neurons. These results indicate that
GABAARs are regulated by FMRP through both an up-regulation of GABAAR expression and a PTEN enhancement-induced inhibition of
GABAAR function, suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP underlies the pathogenesis of
FXS. (IJPPP1307006).

Keywords: Fragile X syndrome, fragile X mental retardation protein, GABAA receptor, PTEN

Address correspondence to: Dr. Qi Wan, Department of Physiology, School of Medicine, Wuhan University, 185 Donghu Road, Wuhan
430071, China. Tel: 027-68759392; Fax: 027-68758766; E-mail: qwan@whu.edu.cn