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Updated: Aug 11, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Activated radixin is essential for GABAA receptor alpha5 subunit anchoring at the actin cytoskeleton
Sven Loebrich1, Robert Bähring, Tatsuya Katsuno
1Zentrum für Molekulare Neurobiologie Hamburg (ZMNH), Universität Hamburg, Hamburg, Germany.
Abstract:
Neurotransmitter receptor clustering is thought to represent a critical parameter for neuronal transmission. Little is known about the mechanisms that anchor and concentrate inhibitory neurotransmitter receptors in neurons. GABAA receptor (GABAAR) alpha5 subunits mainly locate at extrasynaptic sites and are thought to mediate tonic inhibition. Notably, similar as synaptic GABAARs, these receptor subtypes also appear in cluster formations at neuronal surface membranes and are of particular interest in cognitive processing. GABAAR alpha5 mutation or depletion facilitates trace fear conditioning or improves spatial learning in mice, respectively. Here, we identified the actin-binding protein radixin, a member of the ERM family, as the first directly interacting molecule that anchors GABAARs at cytoskeletal elements. Intramolecular activation of radixin is a functional prerequisite for GABAAR alpha5 subunit binding and both depletion of radixin expression as well as replacement of the radixin F-actin binding motif interferes with GABAAR alpha5 cluster formation. Our data suggest radixin to represent a critical factor in receptor localization and/or downstream signaling.
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