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Direct binding of GABA(A) receptor β2 and β3 subunits to gephyrin.
MedLine Citation:
PMID:  23205938     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
GABAergic transmission is essential to brain function, and a large repertoire of GABA type A receptor (GABA(A) R) subunits is at a neuron's disposition to serve this function. The glycine receptor (GlyR)-associated protein gephyrin has been shown to be essential for the clustering of a subset of GABA(A) R. Despite recent progress in the field of gephyrin-dependent mechanisms of postsynaptic GABA(A) R stabilisation, the role of gephyrin in synaptic GABA(A) R localisation has remained a complex matter with many open questions. Here, we analysed comparatively the interaction of purified rat gephyrin and mouse brain gephyrin with the large cytoplasmic loops of GABA(A) R α1, α2, β2 and β3 subunits. Binding affinities were determined using surface plasmon resonance spectroscopy, and showed an ~ 20-fold lower affinity of the β2 loop to gephyrin as compared to the GlyR β loop-gephyrin interaction. We also probed in vivo binding in primary cortical neurons by the well-established use of chimaeras of GlyR α1 that harbour respective gephyrin-binding motifs derived from the different GABA(A) R subunits. These studies identify a novel gephyrin-binding motif in GABA(A) R β2 and β3 large cytoplasmic loops.
Authors:
Sarah Kowalczyk; Aline Winkelmann; Birthe Smolinsky; Benjamin Förstera; Ines Neundorf; Guenter Schwarz; Jochen C Meier
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  The European journal of neuroscience     Volume:  -     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.
Affiliation:
Department of Chemistry, Institute of Biochemistry, University of Cologne, Cologne, Germany; Center for Molecular Medicine, University of Cologne, Cologne, Germany.
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