Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin

Hans Michael Maric, Vikram Babu Kasaragod, Torben Johann Hausrat, Matthias Kneussel, Verena Tretter, Kristian Strømgaard and Hermann Schindelin ()
Additional contact information
Hans Michael Maric: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg
Vikram Babu Kasaragod: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg
Torben Johann Hausrat: Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf
Matthias Kneussel: Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf
Verena Tretter: Medical University Vienna
Kristian Strømgaard: University of Copenhagen
Hermann Schindelin: Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract γ-Aminobutyric acid type A and glycine receptors (GABAARs, GlyRs) are the major inhibitory neurotransmitter receptors and contribute to many synaptic functions, dysfunctions and human diseases. GABAARs are important drug targets regulated by direct interactions with the scaffolding protein gephyrin. Here we deduce the molecular basis of this interaction by chemical, biophysical and structural studies of the gephyrin–GABAAR α3 complex, revealing that the N-terminal region of the α3 peptide occupies the same binding site as the GlyR β subunit, whereas the C-terminal moiety, which is conserved among all synaptic GABAAR α subunits, engages in unique interactions. Thermodynamic dissections of the gephyrin–receptor interactions identify two residues as primary determinants for gephyrin’s subunit preference. This first structural evidence for the gephyrin-mediated synaptic accumulation of GABAARs offers a framework for future investigations into the regulation of inhibitory synaptic strength and for the development of mechanistically and therapeutically relevant compounds targeting the gephyrin–GABAAR interaction.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms6767 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6767

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms6767

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().