Skip to Content
MilliporeSigma
  • Reduced synaptic function of Kainate receptors in the insular cortex of Fmr1 Knock-out mice.

Reduced synaptic function of Kainate receptors in the insular cortex of Fmr1 Knock-out mice.

Molecular brain (2018-09-23)
Shuang Qiu, Yu Wu, Xinyou Lv, Xia Li, Min Zhuo, Kohei Koga
ABSTRACT

Fragile X syndrome is caused by the loss of fragile X mental retardation protein (FMRP). Kainate receptor (KAR) is a subfamily of ionotropic glutamate receptors (iGluR) that acts mainly as a neuromodulator of synaptic transmission and neuronal excitability. However, little is known about the changes of synaptic KAR in the cortical area of Fmr1 KO mice. In this study, we performed whole-cell patch-clamp recordings from layer II/III pyramidal neurons in the insular cortex of Fmr1 KO mice. We found that KARs mediated currents were reduced in Fmr1 KO mice. KARs were mainly located in the synaptosomal fraction of the insular cortex. The abundance of KAR subunit GluK1 and GluK2/3 in the synaptosome was reduced in Fmr1 KO mice, whereas the total expressions of these KARs subunits were not changed. Finally, lack of FMRP impairs subsequent internalization of surface GluK2 after KAR activation, while having no effect on the surface GluK2 expression. Our studies provide evidence indicating that loss of FMRP leads to the abnormal function and localization of KARs. This finding implies a new molecular mechanism for Fragile X syndrome.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
CNQX, ≥98% (HPLC), solid
Sigma-Aldrich
Anti-NMDAR2A Antibody, serum, Chemicon®
Sigma-Aldrich
Anti-Actin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-NMDAR2B Antibody, pain, serum, Chemicon®
Sigma-Aldrich
Anti-GluR6/7 Antibody, clone NL9, rabbit monoclonal, culture supernatant, clone NL904, Upstate®
Sigma-Aldrich
Anti-GluR5 Antibody, Upstate®, from rabbit