Abnormal AMPA receptor trafficking in a mouse model of fragile X syndrome

• Autorzy: Chojnacka M. , Beroun A. , Kuzniewska B. , Kaczmarek L. , Dziembowska M.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Fragile X syndrome (FXS) a common inherited form of mental retardation and autism is caused by lack of expression of fragile X mental retardation protein (FMRP). FMRP is RNA-binding protein that regulates local translation of many synaptic proteins, including AMPA-type glutamate receptors subunits. Accumulated evidence indicate that proper rates of exocytosis and endocytosis of glutamate receptors play a key role in synaptic plasticity. However, current state of knowledge of AMPA receptor trafficking in FXS models is incomplete. AIM(S): The aim of this study was to analyze AMPA receptor trafficking in a mouse model of fragile X syndrome. METHOD(S): We used synaptoneurosomes (SN) isolated from Fmr1 KO and wild-type (WT) mice and stimulated them in vitro with NMDA/glutamate. To determine levels of surface and intracellular GluR1, GluR2 and GluR3 we used crosslinking of SN with BS3 reagent followed by western blot analysis. To confirm our biochemical results we investigated the synaptic calcium-permeable AMPA receptors using whole-cell patch-clamp recordings. RESULTS: We found that SN stimulation produced an increase in the surface glutamate receptor subunits only in WT mice. We also found that surface GluR2 protein level was significantly higher in Fmr1 KO SN in basal conditions, when compared to WT. The electrophysiological experiments confirmed higher abundance of GluR2‑containing AMPA receptors in the hippocampus of Fmr1 KO mice. CONCLUSIONS: Our results indicate that Fmr1 KO mice exhibit abnormal AMPA receptor trafficking and it is demonstrated by elevated amount GluR2.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.63-64

Twórcy

autor

Chojnacka M.

• Laboratory of RNA Biology and Functional Genomics, Institute of Biochemistry and Biophysics, Warsaw, Poland
• Laboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, Poland

autor

Beroun A.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Kuzniewska B.

• Laboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, Poland

autor

Kaczmarek L.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Dziembowska M.

• Laboratory of Molecular Basis of Synaptic Plasticity, Centre of New Technologies, University of Warsaw, Warsaw, Poland