Direct binding of GABA(A) receptor β2 and β3 subunits to gephyrin

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Item Type:	Article
Title:	Direct binding of GABA(A) receptor β2 and β3 subunits to gephyrin
Creators Name:	Kowalczyk, S., Winkelmann, A., Smolinsky, B., Foerstera, B., Neundorf, I., Schwarz, G. and Meier, J.C.
Abstract:	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 {alpha}1, {alpha}2, {beta}2 and {beta}3 subunits. Binding affinities were determined using surface plasmon resonance spectroscopy, and showed an ~ 20-fold lower affinity of the {beta}2 loop to gephyrin as compared to the GlyR {beta} loop-gephyrin interaction. We also probed in vivo binding in primary cortical neurons by the well-established use of chimaeras of GlyR {alpha}1 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 {beta}2 and {beta}3 large cytoplasmic loops.
Keywords:	beta Subunit, Clustering, GABAA Receptor, Gephyrin, Phosphorylation, Animals, Mice, Rats
Source:	European Journal of Neuroscience
ISSN:	0953-816X
Publisher:	Wiley-Blackwell
Volume:	37
Number:	4
Page Range:	544-554
Date:	February 2013
Official Publication:	https://doi.org/10.1111/ejn.12078
PubMed:	View item in PubMed

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